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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.

Take Home Messages Among men with low- or intermediate-risk prostate cancer who choose active surveillance, those with suspicious magnetic resonance imaging (MRI) at the time of inclusion in active surveillance are more likely to show switch to treatment than men with nonsuspicious MRI., Background The inclusion criterion for active surveillance (AS) is low- or intermediate-risk prostate cancer. The predictive value of the presence of a suspicious lesion at magnetic resonance imaging (MRI) at the time of inclusion is insufficiently known. Objective To evaluate the percentage of patients needing active treatment stratified by the presence or absence of a suspicious lesion at baseline MRI. Design, setting, and participants A retrospective analysis of the data from the multicentric AS GAP3 Consortium database was conducted. The inclusion criteria were men with grade group (GG) 1 or GG 2 prostate cancer combined with prostate-specific antigen

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.

Consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) remains controversial, with routine practice continuing to include RT in patients with initial bulky disease or residual masses. Positron emission tomography (PET)-computed tomography is a sensitive modality for detecting the presence of residual disease at the end of treatment (EOT). A PET-guided approach to selectively administering RT has been the policy in British Columbia since 2005. Patients with advanced-stage DLBCL diagnosed from 1 January 2005 to 1 March 2017 and treated with at least 6 cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab), who underwent EOT PET, were included in this analysis. Those with complete metabolic response (PET-negative [PET-NEG]) were observed; those with PET-positive (PET-POS) scans were offered consolidative RT, when feasible. Of the patient records reviewed, 723 were identified, with median follow-up of 4.3 years: 517 (72%) were PET-NEG; 206 (28%) were PET-POS. Time to progression (TTP) and overall survival (OS) at 3 years were 83% vs 56% and 87% vs 64%, in patients with PET-NEG and PET-POS scans, respectively. PET-POS patients with nonprogressing disease treated with consolidative RT (109 and 206; 53%) had outcomes approaching those of PET-NEG patients, with 3-year estimates of 76% and 80% for TTP and OS. PET-NEG patients who had bulky disease (≥10 cm) at diagnosis had outcomes indistinguishable from those without bulk, despite the omission of RT. These data suggest that patients with advanced-stage DLBCL who are PET-NEG at EOT and receive no RT have excellent outcomes. 18F-fluorodeoxyglucose-PET can reliably guide selective administration of consolidative RT, even in patients with initially bulky disease.

Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

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.

Androgen deprivation therapy is an established therapy for castration sensitive prostate cancer and recent studies have observed that patients whose testosterone levels are suppressed below 0.7 nmol/l have improved outcomes. Testosterone breakthrough, or a rise in testosterone above a target threshold after the first month of androgen deprivation therapy, is generally associated with treatment deficiency. The purpose of this review is to summarize breakthrough rate data and explore the relationship to clinical outcomes in patients with castration sensitive prostate cancer receiving androgen deprivation therapy.Our systematic search identified 45 studies with a total of 52 cohorts representing 6,047 total patients reporting testosterone breakthrough rates or derivative measures above the thresholds of 1.7 nmol/l (51 cohorts, 6,015 patients) or 0.7 nmol/l (15 cohorts, 2,495 patients).Significantly higher weighted mean breakthrough rates were seen for the 0.7 nmol/l threshold compared to 1.7 nmol/l (41.3% vs 6.9%, p0.0001). A significant association between breakthrough rates and worse clinical outcomes overall was not found, although when larger trials (sample size greater than 100) and higher event rates (greater than 50%) were considered for the lowest threshold, significant associations between breakthrough rates and clinical outcomes were observed. Clinical factors such as administration and monitoring frequency, type of testosterone assay and type of androgen deprivation therapy did not significantly affect breakthrough rates, although nonvalidated assays were associated with a large degree of variability.Results from our analysis indicate that testosterone breakthroughs likely result in worse clinical outcomes and should be avoided. Moreover, there is a need to standardize assessment of testosterone levels both clinically and in the research context to better inform treatment decisions and improve the reliability and comparability of results across studies.

With a median follow-up of 16.6 years, Lo and colleagues report excellent long-term outcomes with primary radiotherapy for limited-stage follicular lymphoma in this month’s CME article.

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.

Background Men with prostate cancer (PCa) on active surveillance (AS) are followed through regular prostate biopsies, a burdensome and often unnecessary intervention, not without risks. Identifying men with at a low risk of disease reclassification may help reduce the number of biopsies. Objective To assess the external validity of two Canary Prostate Active Surveillance Study Risk Calculators (PASS-RCs), which estimate the probability of reclassification (Gleason grade ≥7 with or without >34% of biopsy cores positive for PCa) on a surveillance biopsy, using a mix of months since last biopsy, age, body mass index, prostate-specific antigen, prostate volume, number of prior negative biopsies, and percentage (or ratio) of positive cores on last biopsy. Design, setting, and participants We used data up to November 2017 from the Movember Foundation’s Global Action Plan (GAP3) consortium, a global collaboration between AS studies. Outcome measurements and statistical analysis External validity of the PASS-RCs for estimating reclassification on biopsy was assessed by calibration, discrimination, and decision curve analyses. Results and limitations Five validation cohorts (Prostate Cancer Research International: Active Surveillance, Johns Hopkins, Toronto, Memorial Sloan Kettering Cancer Center, and University of California San Francisco), comprising 5105 men on AS, were eligible for analysis. The individual cohorts comprised 429–2416 men, with a median follow-up between 36 and 84 mo, in both community and academic practices mainly from western countries. Abilities of the PASS-RCs to discriminate between men with and without reclassification on biopsy were reasonably good (area under the receiver operating characteristic curve values 0.68 and 0.65). The PASS-RCs were moderately well calibrated, and had a greater net benefit than most default strategies between a predicted 10% and 30% risk of reclassification. Conclusions Both PASS-RCs improved the balance between detecting reclassification and performing surveillance biopsies by reducing unnecessary biopsies. Recalibration to the local setting will increase their clinical usefulness and is therefore required before implementation. Patient summary Unnecessary prostate biopsies while on active surveillance (AS) should be avoided as much as possible. The ability of two calculators to selectively identify men at risk of progression was tested in a large cohort of men with low-risk prostate cancer on AS. The calculators were able to prevent unnecessary biopsies in some men. Usefulness of the calculators can be increased by adjusting them to the characteristics of the population of the clinic in which the calculators will be used.

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.

Take Home Message Risks of upgrading and disease progression were higher among African than among Caucasian men on active surveillance for prostate cancer. Transitioning to treatment without progression was highest among Asian men. Understanding of the reasons for these differences requires further investigation., Background Studies of active surveillance (AS) for prostate cancer (PCa) have focussed predominantly on Caucasian populations. Little is known about the experience of Asian men, while suitability for men of African descent has been questioned. Objective To compare baseline characteristics, follow-up, and outcomes for men on AS for PCa, according to ethnicity. Design, setting, and participants The study cohort included 13 centres from the GAP3 consortium that record ethnicity (categorised broadly as Caucasian/white, African/Afro-Caribbean/black, Asian, mixed/other, and unknown). Men with biopsy grade group >2, prostate-specific antigen (PSA) >20 ng/ml, T stage ≥cT3, or age >80 yr were excluded. Outcome measurements and statistical analysis Clinical characteristics, follow-up schedules, outcome status, and reasons for discontinuation were compared across ethnic groups. Risk of upgrading, potential disease progression (grade group ≥3 or T stage ≥3), suspicious indications (any upgrading, number of positive cores >3, T stage ≥cT3, PSA >20 ng/ml, or PSA density >0.2 ng/ml/cc2), and conversion to treatment were assessed using mixed-effect regression models. Results and limitations The eligible cohort (n = 9158) comprised 83% Caucasian men, 6% men of African descent, 5% Asian men, 2% men of mixed/other ethnicity, and 4% men of unknown ethnicity. Risks of suspicious indicators (hazard ratio = 1.27; 95% confidence interval [CI] 1.12–1.45), upgrading (odds ratio [OR] = 1.40; 95% CI 1.14–1.71), and potential progression (OR = 1.46; 95% CI 1.06–2.01) were higher among African/black than among Caucasian/white men. Risk of transitioning to treatment did not differ by ethnicity. More Asian than Caucasian men converted without progression (42% vs 26%, p < 0.001). Heterogeneity in surveillance protocols and racial makeup limit interpretation. Conclusions This multinational study found differences in the risk of disease progression and transitioning to treatment without signs of progression between ethnic groups. Further research is required to determine whether differences are due to biology, sociocultural factors, and/or clinical practice. Patient summary This international study compared prostate cancer active surveillance outcomes by ethnicity. Risks of upgrading and disease progression were higher among African than among Caucasian men. Transitioning to treatment without progression was highest among Asian men. Understanding of these differences requires further investigation.

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.

Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold.A total of 2,339 patients with low or intermediate risk prostate cancer receivedAt a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort.Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.

Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma, with 8% of patients presenting with stage II disease. Stage II FL is potentially curable with radiation therapy (RT), but more than half of patients relapse within 10 years. The Ann Arbor stage II definition encompasses a broad spectrum of disease extents and distributions; understanding how these factors affect outcomes could enable identification of patients at higher risk for progression. The purpose of this study was to investigate the impact of disease extent and distribution on outcomes in stage II FL. Methods: The study included patients who were diagnosed with stage II or IIE, grade 1-3A FL from 1980 to 2016 at BC Cancer, had non-mesenteric disease, and were treated with curative-intent (≥ 20 Gy) RT alone. Our provincial recommendation was to use curative-intent RT for limited-stage patients, with limited stage defined as stage I or II, non-bulky, radio-encompassable disease with no B symptoms. Prior to February 1998, the provincial policy was to use involved regional RT. In March 1998, the policy was changed to use involved-site RT. Medical records were retrospectively reviewed for patient, disease, and treatment characteristics and outcomes. Survival estimates were calculated using the Kaplan-Meier method starting from the diagnosis date. Events were defined as relapse for freedom from progression (FFP), relapse or death from any cause for progression-free survival (PFS), death due to FL or FL treatment for disease-specific survival (DSS), and death from any cause for overall survival (OS). Univariable analyses (UVA) were performed using the log-rank test, and multivariable analyses (MVA) were performed using the Cox proportional hazards model. Results were considered significant if p ≤ 0.05. Results: 222 patients were diagnosed with stage II, grade 1-3A FL from 1980 to 2016. 56 patients were excluded due to mesenteric involvement. Of the 166 remaining non-mesenteric patients, 16 were excluded due to treatment with chemoimmunotherapy only, 28 due to combined modality therapy, 3 due to palliative RT, 19 due to management with watchful waiting, and 1 due to treatment refusal. The remaining 99 patients formed our study cohort. The median follow-up duration of living patients was 13.6 years (range, 4.8-35.4). The median age at diagnosis was 59.5 years (range, 33.2-86.2), and 56% of patients were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 68% of patients and 1-2 in 34%. 18% of patients had extranodal disease, 11% had grade 3A disease, 4% had complete resection of disease prior to RT, and 2% had elevated lactate dehydrogenase (LDH). The median greatest diameter of any individual mass was 3.6 cm. 11% had 1 involved lymph node region (staged as IIE due to extranodal disease), 64% had 2 regions, 18% had 3 regions, and 7% had 4 regions. Table 1 shows the FFP, PFS, DSS, and OS at 5, 10, and 15 years for the study cohort. Of the 57 patients who relapsed, 1 (2%) had in-field relapse only, 1 (2%) had in-field and marginal relapse, 9 (16%) had in-field and distant (± marginal) relapse, 2 (4%) had marginal relapse only, 7 (12%) had marginal and distant relapse, 36 (63%) had distant relapse only, and 1 (2%) had unknown site(s) of relapse. On UVA (Table 2), age ≥ 60 years was associated with inferior DSS and OS; greatest diameter ≥ 3.5 cm was associated with inferior FFP and PFS (Figure 1A and 1B); disease involving the paraaortic region was associated with inferior FFP and PFS; and involvement of 4 lymph node regions was associated with inferior PFS (Figure 1D). On MVA (Table 3), greatest diameter ≥ 3.5 cm and involvement of 4 lymph node regions were associated with an inferior FFP and PFS, while older age was associated with an inferior DSS and OS. Bilateral disease, infradiaphragmatic disease, and extranodal involvement did not correlate with worse outcomes on UVA or MVA. Conclusions: Greatest diameter of disease ≥ 3.5 cm and involvement of 4 lymph node regions are significantly associated with inferior FFP and PFS in stage II FL patients with non-mesenteric disease and treated with curative-intent RT alone. Bilateral disease, infradiaphragmatic disease, and extranodal involvement are not associated with worse outcomes. These results may assist clinicians with identifying specific patients in this population at higher risk for progression, facilitating improved treatment decision-making and patient counselling. Figure 1 Figure 1. Disclosures Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Scott: Janssen: Consultancy, Research Funding; Rich/Genentech: Research Funding; NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling.; BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling--licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling. ; Abbvie: Consultancy; Incyte: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy. Villa: Janssen: Honoraria; Roche: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Seattle Genetics: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; NanoString Technologies: Honoraria. Gerrie: Janssen: Honoraria, Research Funding; Sandoz: Honoraria; AbbVie: Honoraria, Research Funding; Astrazeneca: Honoraria, Research Funding; Roche: Research Funding. Savage: Roche: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding; BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding; Takeda: Other: Institutional clinical trial funding; Beigene: Other: Institutional clinical trial funding; Genentech: Research Funding.

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.

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for

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.

Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors.We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate (125)I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation.At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas.Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.

Joint modelling of longitudinal and survival data is increasingly used in clinical trials on cancer. In prostate cancer for example, these models permit to account for the link between longitudinal measures of prostate-specific antigen (PSA) and time of clinical recurrence when studying the risk of relapse. In practice, multiple types of relapse may occur successively. Distinguishing these transitions between health states would allow to evaluate, for example, how PSA trajectory and classical covariates impact the risk of dying after a distant recurrence post-radiotherapy, or to predict the risk of one specific type of clinical recurrence post-radiotherapy, from the PSA history. In this context, we present a joint model for a longitudinal process and a multi-state process, which is divided into two sub-models: a linear mixed sub-model for longitudinal data and a multi-state sub-model with proportional hazards for transition times, both linked by a function of shared random effects. Parameters of this joint multi-state model are estimated within the maximum likelihood framework using an EM algorithm coupled with a quasi-Newton algorithm in case of slow convergence. It is implemented under R, by combining and extending mstate and JM packages. The estimation program is validated by simulations and applied on pooled data from two cohorts of men with localized prostate cancer. Thanks to the classical covariates available at baseline and the repeated PSA measurements, we are able to assess the biomarker's trajectory, define the risks of transitions between health states and quantify the impact of the PSA dynamics on each transition intensity. Copyright © 2016 John Wiley & Sons, Ltd.

Background The Prostate Cancer Research International Active Surveillance (PRIAS) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance (AS). Objective We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy (RP). Design, setting, and participants Men with low-risk prostate cancer were included and followed prospectively on AS. Follow-up consisted of regular prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies. Men with Gleason >3+3, more than two positive biopsy cores, or stage higher than cT2 were advised to switch to active treatment (until 2014, a PSA doubling time [PSA DT] of 0–3 yr was also used). Outcome measurements and statistical analysis Reclassification rates, treatment after discontinuation, and outcome on RP after discontinuing AS were reported. Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment. Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points. Results and limitations A total of 5302 men were included in PRIAS across 18 countries. Reclassification rates remained stable on all subsequent biopsies, with 22–33% of men having either Gleason >3+3 or more than two positive cores on any repeat biopsy. At 5 and 10 yr of follow-up, 52% and 73% of men, respectively, had discontinued AS, most of them because of protocol-based reclassification. A third of men undergoing subsequent RP had favorable pathologic tumor features (Gleason 3+3 and pT2). Of the criteria used to recommend a switch to active treatment, more than two positive cores and a PSA DT of 0–3 yr were not predictive of unfavorable pathologic outcome on RP. Conclusions A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP; therefore, we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment. Surrogate indicators (eg, more than two positive cores and a fast-rising PSA) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease. Patient summary We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer; however, some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance.

Introduction: Limited stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a highly curable malignancy with an excellent prognosis. Given disease rarity, there are few prospective studies and as a result, diverse treatment approaches are used in both the adult and pediatric populations. At BC Cancer, provincial treatment guidelines for limited stage NLPHL have largely followed that of classical HL: Prior to 2005, radiotherapy (RT) was integrated usually as combined modality therapy (CMT); after 2005, an adaptive approach using 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was adopted. Herein, we evaluated the impact of using this approach. Methods: Adult (>16 years [y]) patients (pts) diagnosed with limited stage NLPHL (stage 1A, 1B or 2A, non-bulky [ Results: A total of 98 pts were identified. Of these, 93 (95%) received active therapy. Patient characteristics did not differ between the two eras: median age 38 y (range 16 - 82 y); male n=73 (74%); stage 2 n=43 (44%); median largest mass size 4 cm (range 2 - 9 cm). In the CMT era (n=37), all pts received active therapy: 84% were treated with ABVD (like) CHT (ABVD n=30 [including ABVD alone n=2], MOPP/ABV n=1); 6 pts with stage 1A received RT alone. In the PET era (n=61), 92% received active therapy (n=56), of which 52 received CHT (ABVD n=49, modified CVPP/ABO with bleomycin omitted n=1, R-CHOP n=2) and 4 pts were treated with RT alone. The remaining 5 pts were observed/refused therapy. With a median follow up of 7.7 y for all pts (range 0.3 - 20.5 y) (CMT era 13.5 y [3.3 - 20.5 y], PET era 5.5 y [0.3 - 13.5 y]), the time to progression (TTP), progression free survival (PFS), overall survival (OS), and disease specific survival (DSS) at 5 y were 93%, 92%, 98%, and 99%, respectively. There was no difference in outcomes by era comparison (p >0.1) or by stage (1 vs 2) (p=0.93). Overall, there have been 7 lymphoma recurrences (CMT era n=3, PET era n=4), including 3 (3%) with transformed disease (biopsy proven T cell rich B cell lymphoma n=1, presumed aggressive lymphomas based on new splenic nodules n=2). In total, there were 48/52 cases that had a PET2 scan interpreted using the D criteria, including 30 in the IHP time period that were re-reviewed: 85% were PETneg (n=41); 15% were PETpos (n=7). Four CHT treated pts did not receive a PET2 scan: RT added (CHT toxicity) n=3; death (diabetic ketoacidosis [DKA] post cycle 1 ABVD) n=1. All PETpos cases and only 4 PETneg cases (CHT toxicity n=2, PETpos by IHP criteria n=2) received RT. Considering PET-specific outcomes, the 5 y PFS and TTP were both 92% for PETneg and 80% for PETpos cases (p=0.56) (Figure 1). Three recurrences occurred in PETneg pts (DX n=1, D2 n=2), all of which had received ABVD alone but only 1 would have been solely in a RT field. The single recurrence among the PETpos cases (D5) was outside of the RT field. In the whole cohort, 9 pts have died (CMT era n=5, PET era n=4). Two deaths in the PET era were deemed related to NLPHL: 1 patient refused primary therapy and died of progressive disease and the other died during ABVD of DKA, possibly treatment related. The remaining deaths were due to other malignancies (lung n=2 [one within RT field], vulvar n=1, anaplastic large cell lymphoma n=1) or unknown causes (n=3). Conclusions: Consistent with other modern series, the outcome of pts with limited stage NLPHL is excellent with both 5 y PFS and OS exceeding 90%. Pts with an interim PETneg scan have a favorable outcome although longer follow-up is needed given the long natural history of NLPHL. This represents the largest experience of a PET-adapted approach in NLPHL and supports that ABVD alone is a viable option in selected patients with consideration of both acute and long term toxicities. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Scott:Celgene: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Astellas Inc.: Research Funding; Abbvie, Sanofi: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria. Connors:Takeda Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding.

Background: Treatment practices for patients with limited-stage DLBCL are varied and include combined-modality treatment (3 cycles immunochemotherapy + radiation therapy) or immunochemotherapy alone. Since 2005, patients (pts) in BC with limited-stage DLBCL (stage I/II, no B-symptoms, mass < 10cm) have been treated according to a PET-guided algorithm. Following 3 cycles of R-CHOP, pts undergo FDG-PET/CT scan; PET-negative pts receive one additional cycle of R-CHOP, while PET-positive pts receive involved-site radiation therapy (RT). We present long-term follow-up of this population-based experience. Methods: Using the BC Cancer Lymphoid Cancer Database we identified all pts who were diagnosed with limited-stage DLBCL from Mar 2005 to February 2019 and underwent a PET/CT after 3 cycles of curative-intent R-CHOP, in keeping with the PET-guided policy. Pts with primary CNS, primary testicular, PMBCL, PTLD, and transformed/discordant/composite lymphoma were excluded. Pts with evidence of progressive disease prior to or on mid-treatment PET/CT were also excluded. All PET/CT scans were performed and reviewed centrally. Prior to 2014, interpretation was based on the International Harmonization Project (IHP) criteria, and subsequently according to Deauville criteria. Importantly, uptake greater than the mediastinal blood pool was consistently used to determine PET-positivity (ie. PET-positive by IHP, or D3-5 by Deauville). Results: Clinical characteristics of the 319 pts identified are as follows: median age, 68 y (range 19-92); 48%, male; 59%, stage I; 41%, stage II; 8%, PS>1; 13%, elevated LDH; 52%, at least 1 extranodal site; 37%, mass size ≥ 5cm. Stage-modified IPI risk score: 19%, 0; 45%, 1; 27%, 2; 9%, 3-4. Median follow-up is 6.25 yrs (range 0.42-14.25). After 3 cycles of R-CHOP: 254 pts (80%) were PET-negative; 59 pts (18%) were PET-positive; and 6 pts (2%) were considered PET-indeterminate (by IHP). Elevated serum LDH (p4 years from diagnosis. Of the 6 PET-indeterminate patients, 2 received RT and 3/6 have relapsed. Overall 5-year time-to-progression (TTP) censoring deaths from unrelated causes is 89% (92% for PET-negative and 80% for PET-positive pts). Overall 5-year PFS is 84% (88% for PET-negative and 74% for PET-positive pts) and 5-year OS is 87% (90% for PET-negative and 77% for PET-positive pts). On univariate analysis, age>60, PS>1, stage-modified IPI, and PET status were significant predictors of TTP. On multivariate analysis controlling for age>60, stage, PS, LDH, presence of extranodal involvement, mass size ≥ 5cm, and PET status, only age (p=0.002) and PET status (p=0.004) remained independent predictors of TTP. Conclusion: Using a PET-guided approach to treatment, the majority of patients with limited-stage DLBCL have negative PET scans after 3 cycles of R-CHOP. Patients with negative PET scans have an excellent outcome when treated with 4 cycles of R-CHOP alone, without exposure to radiation. Patients with a positive PET scan who complete treatment with radiation therapy have a slightly less favorable outcome, and may be appropriate for alternative approaches. A detailed analysis of patterns of relapse, as well as efforts to identify clinical factors, PET parameters and biomarkers associated with poor outcome and delayed relapse are ongoing. Figure Disclosures Sehn: Acerta: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria. Scott:NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Abbvie, Sanofi: Consultancy, Honoraria; Astellas Inc.: Research Funding. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria.

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

Background and Purpose: To report outcomes and toxicity after proton beam radiotherapy for non-peripapillary choroidal and ciliary body melanoma considered unsuitable for other eye-sparing therapies. Materials and Methods: An existing database of 77 patients with non-peripapillary tumors treated at TRIUMF, Canada, including patient, tumor, and treatment characteristics, was updated with ocular complications and follow-up status from chart reviews. Results: Most of the patients had large tumors: 61% were T3/T4 tumors (AJCC classification), while 48% were large by the Collaborative Ocular Melanoma Study classification. The median thickness was 7.1 mm, and the ciliary body was involved in 35%. After 5 and 10 years, the actuarial ocular tumor control rate was 85 and 85%, metastasis-free survival was 72 and 57%, overall survival was 77 and 63%, the enucleation rate was 22 and 22%, and complete blindness was found in 38 and 38%, respectively. On univariate analysis, patients with ciliary body involvement had significantly worse metastasis-free survival and overall survival rates compared to patients without ciliary body involvement (p < 0.001). Conclusions: Proton therapy for large anteriorly located tumors resulted in acceptable ocular tumor control and survival rates. The risk of blindness and severe toxicity requiring enucleation was low, and a substantial proportion of patients maintained useful vision.

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.