OBJECTIVES:To evaluate the treatment patterns and outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride in the UK. METHODS:Patients initiating treatment with radium-223 from 1 September 2017 to 1 September 2019 in 15 UK oncology centres were included. Demographics, treatment, clinical, biochemical, and outcome data were collected prospectively. Quality of life data were obtained using analgesic scores and components of the Functional Assessment Cancer Therapy - Prostate (FACT-P) questionnaire. RESULTS:A total of 550 consecutive, evaluable patients were included. The most common prior therapy for mCRPC was enzalutamide. At final analysis, after a median follow-up of 13.3 months, 55% of patients had completed six cycles of treatment. Median overall survival was 13.7 months (95% confidence interval, 12.6-14.8 months). Poor performance status, prior use of docetaxel in the metastatic hormone sensitive prostate cancer (mHSPC) setting, number of lines of prior treatment, and abnormal platelet count were independent variables associated with poor prognosis. Adverse events led to treatment discontinuation in 5.5% of patients. WHO analgesic scores and FACT-P questionnaire scores did not significantly change after treatment administration. CONCLUSION:The National Radium-223 Dichloride Audit was the first and largest multicentre prospective analysis of treatment patterns, outcomes, and quality of life data in patients treated with radium-223 in the UK. Radium-223 can be administered safely to patients previously treated with other life-prolonging therapies. Efficacy and safety data compare favourably with clinical trial and other real-world data. Our results suggest that its use earlier in the treatment pathway is associated with longer survival.

BACKGROUND:Radium-223 and taxane chemotherapy each improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). Whether the radium-223-taxane sequence could extend survival without cumulative toxicity was explored. METHODS:The global, prospective, observational REASSURE study (NCT02141438) assessed real-world safety and effectiveness of radium-223 in patients with mCRPC. Using data from the prespecified second interim analysis (data cutoff, March 20, 2019), hematologic events and overall survival (OS) were evaluated in patients who were chemotherapy-naive at radium-223 initiation and subsequently received taxane chemotherapy starting ≤90 days ("immediate") or >90 days ("delayed") after the last radium-223 dose. RESULTS:Following radium-223 therapy, 182 patients received docetaxel (172 [95%]) and/or cabazitaxel (44 [24%]); 34 patients (19%) received both. Seventy-three patients (40%) received immediate chemotherapy and 109 patients (60%) received delayed chemotherapy. Median time from last radium-223 dose to first taxane cycle was 3.6 months (range, 0.3-28.4). Median duration of first taxane was 3.7 months (range, 0-22.0). Fourteen patients (10 in the immediate and four in the delayed subgroup) had grade 3/4 hematologic events during taxane chemotherapy, including neutropenia in two patients in the delayed subgroup and thrombocytopenia in one patient in each subgroup. Median OS was 24.3 months from radium-223 initiation and 11.8 months from start of taxane therapy. CONCLUSIONS:In real-world clinical practice settings, a heterogeneous population of patients who received sequential radium-223-taxane therapy had a low incidence of hematologic events, with a median survival of 1 year from taxane initiation. Thus, taxane chemotherapy is a feasible option for those who progress after radium-223. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov identifier NCT02141438. PLAIN LANGUAGE SUMMARY:Radium-223 and chemotherapy are treatment options for metastatic prostate cancer, which increase survival but may affect production of blood cells as a side effect. We wanted to know what would happen if patients received chemotherapy after radium-223. Among the 182 men treated with radium-223 who went on to receive chemotherapy, only two men had severe side effects affecting white blood cell production (neutropenia) during chemotherapy. On average, the 182 men lived for 2 years after starting radium-223 and 1 year after starting chemotherapy. In conclusion, patients may benefit from chemotherapy after radium-223 treatment without increasing the risk of side effects.

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophinreleasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided alpha of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 072). Standard time-toevent analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 89 years (70-100), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the longcourse ADT group; HR 0773 [95% CI 0612-0975]; p=0029). 10-year metastasis-free survival was 719% (95% CI 676-757) in the short-course ADT group and 781% (742-815) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.

Background Previous evidence indicates that adjuvant, short -course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high -risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short -course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided alpha of 5% to detect an absolute increase in 10 -year metastasisfree survival from 80% to 86% (hazard ratio [HR] 067). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short -course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 90 years (IQR 71-101), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the shortcourse ADT group; HR 0886 [95% CI 0688-1140], p=035). 10 -year metastasis-free survival was 792% (95% CI 754-825) in the no ADT group and 804% (766-836) in the short -course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short -course ADT group (p=015), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short -course ADT with postoperative radiotherapy in this patient population.

Background and objective: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term. Methods: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of non- protocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles. Key findings and limitations: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison. Conclusions and clinical implications: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Purpose: Emerging data indicate comparable disease control and toxicity of normal postoperative fractionation and moderate hypofractionation radiation therapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66 Gy in 33 fractions (f) over 6.5 weeks or 52.5 Gy in 20f over 4 weeks. This non-randomized, exploratory analysis explored the toxicity of these 2 schedules in patients who had adjuvant RT. Methods and Materials: Information on RT dose was collected in all patients. The Radiation Therapy Oncology Group toxic-ity score was recorded every 4 months for 2 years, every 6 months until 5 years, then annually until 15 years. Patient-reported data were collected at baseline and at 1, 5, and 10 years using standard measures, including the Vaizey fecal incontinence score (bowel) and the International Continence Society Male Short-Form questionnaire (urinary incontinence). The highest event grade was recorded within the first 2 years and beyond 2 years and compared between treatment groups using the chi(2) test. Results: Of 634 patients, 217 (34%) were planned for 52.5 Gy/20f and 417 (66%) for 66 Gy/33f. In the first 2 years, grade 1 to 2 cystitis was reported more frequently among the 66 Gy/33f group (52.5 Gy/20f: 20% vs 66 Gy/33f: 30%; P = .04). After 2 years, grade 1 to 2 cystitis was reported in 16% in the 66-Gy group and 9% in the 52.5-Gy group (P = .08). Other toxic effects were similar in the 2 groups, and very few patients had any grade 3 to 4 toxic effects. Patients reported slightly higher urinary and fecal incontinence scores at 1 year than at baseline, but no clinically meaningful differences were reported between the 52.5 Gy/20f and 66 Gy/33f groups. Patient-reported health was similar at baseline and at 1 year and similar between the 52.5 Gy/20f and 66 Gy/33f groups. Conclusions: Severe toxic effects were rare after prostate bed radiation therapy with either 52.5 Gy/20f or 66 Gy/33f. Only modest differences were recorded in toxic effects or in patient-reported outcomes between these 2 schedules. Crown Copyright (c) 2023 Published by Elsevier Inc. All rights reserved.

132 Background: A key difference between the landmark trials for docetaxel chemotherapy alongside ADT for mHSPC was the addition of prednisolone in the STAMPEDE but not CHAARTED or GETUG-AFU 15 trials, resulting in varied use in clinical practice. Potential toxicity from prolonged steroid use was recognised in a 2020 NHS England safety alert. This retrospective study compared toxicities in patients treated with docetaxel +/- prednisolone. Methods: Electronic notes of patients treated with docetaxel and ADT +/- prednisolone (per consultant preference) Feb 2018 - Sept 2020, were reviewed. Data was collected on common toxicities using CTCAE v5 grading. Analysis of incidence and severity were carried out using paired T-tests and logistic regression due to small sample sizes at each severity grade. Results: Data on 299 patients was collected; 167 received docetaxel and ADT, 132 also received prednisolone. There was no significant difference in the number of cycles completed between the 2 groups; 66.5% (no prednisolone) v 70.4% (with prednisolone) of patients completed 6 cycles (p=0.41). There was a significant difference in both the incidence and severity of anaemia between patients treated +/- prednisolone. There was no significant difference in the incidence of neutropenia or alopecia between patients treated +/- prednisolone, but prednisolone use was predictive of lower severity scores in neutropenia and alopecia. In contrast, there was a significant difference seen in incidence of neuropathy between the 2 groups, with no impact on severity. There was no significant difference in incidence or severity of thrombocytopenia, neutropenic sepsis, fatigue or nausea/vomiting. The prednisolone group had a significant increase in contacts with an advice hotline or general practitioner (p values <0.001). Review of interactions found many were requesting support with administration of prednisolone. Conclusions: These findings suggest limited clinical benefit in the addition of prednisolone to docetaxel and ADT in patients with mHSPC. Prednisolone is associated with significant potential harms e.g., impaired blood glucose and adrenal insufficiency (blood glucose was not routinely recorded in this group). These preliminary findings would benefit from further study with a larger sample size. [Table: see text]

PURPOSE Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI ( v CT) or three scans ( v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (–3.5 to –0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION Surveillance is a safe management approach—advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.

Background: Moderate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information. Objective: To determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up. Design, setting, and participants: A phase III randomised controlled trial recruited from 2002 to 2011. The QoL substudy completed accrual in 2009; participants were followed up to 5 yr after radiotherapy. Analyses used data snapshot taken on August 26, 2016. A total of 71 radiotherapy centres were included in the study (UK, Republic of Ireland, Switzerland, and New Zealand); all 57 UK centres participated in the QoL substudy. CHHiP recruited 3216 men with localised prostate cancer (cT1b-T3aN0M0). Intervention: Conventional (74 Gy/37 fractions/7.4 wk) or hypofractionated radiotherapy (60 Gy/20 fractions/4 wk or 57 Gy/19 fractions/3.8 wk) was delivered with intensity-modulated techniques. Outcome measurements and statistical analysis: University of California Los Angeles Prostate Cancer Index, Short Form 36 and Functional Assessment of Cancer Therapy-Prostate, or Expanded Prostate Cancer Index Composite and Short Form 12 questionnaires were administered at baseline, before radiotherapy, at 10 wk, and at 6, 12, 18, 24, 36, 48, and 60 mo after radiotherapy. The QoL primary endpoint was overall bowel bother. Results and limitations: The QoL substudy recruited 2100 patients; 1141 5-yr forms were available from 1957 patients still alive (58%). There were no statistically significant differences in 5-yr prevalence of overall "moderate or big" bowel bother: 19/349 (5.4%), 29/381 (7.6%), and 21/393 (5.3%) for 74, 60, and 57 Gy, respectively; overall urinary or sexual bother at 5 yr was similar between schedules. Bowel and urinary symptoms remained stable from 2 to 5 yr for all schedules. Some evidence of worsening overall sexual bother from baseline to 5 yr was less likely in the hypofractionated schedules compared with 74 Gy (odds ratios for increase in bother score vs 74 Gy: 0.55 [0.30-0.99], p = 0.009 for 60 Gy, and 0.52 [0.29-0.94], p = 0.004 for 57 Gy). General QoL scores were similar between schedules at 5 yr. Conclusions: Longer follow-up confirms earlier findings, with similar patientreported bowel, urinary, and sexual problems between schedules overall. The continued low incidence of moderate or high bother confirms that moderate hypofractionation should be the standard of care for intermediate-risk localised prostate cancer. Patient summary: We looked at patient-reported outcomes up to 5 yr after treatment in a trial of different radiotherapy schedules for prostate cancer. The findings confirmed that shorter radiotherapy schedules were as safe as standard radiotherapy in terms of bowel, urinary, and sexual problems. Take Home Message: Bowel, urinary, and sexual symptoms were similar between schedules up to 5 yr. The continued low incidence of moderate/high bother confirms that moderate hypofractionated radiotherapy should be considered the standard of care for men with intermediate-risk prostate cancer. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

Background The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. Methods We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA >= 10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA >= 0.1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52.5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4.9 years (IQR 3.0-6.1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1.10, 95% CI 0.81-1.49; p=0.56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0.88, 95% CI 0.58-1.33; p=0.53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4.8 vs 4.0; p=0.0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0.020). Interpretation These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

5542 Background: Ra-223, a targeted alpha therapy, showed a survival benefit and favorable safety profile over 3 years’ (yrs) follow-up in mCRPC pts (ALSYMPCA trial). REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of long-term Ra-223 safety in routine clinical practice in mCRPC pts (planned 7-yr follow-up). Methods: This analysis, based on the second prespecified interim analysis (data cutoff 3-20-2019) of REASSURE (N = 1465), evaluated safety/OS in the pt subset that was chemotherapy-naïve at Ra-223 administration but received subsequent taxane therapy any time after Ra-223 completion. Results: 182 pts received taxane therapy after Ra-223. Most (58%) had unresected primary tumors, 69% had ≥6 metastases, 99% received prior systemic anticancer therapy (Table). 143 (79%) completed 5 or 6 Ra-223 injections. Subsequent anticancer therapies included docetaxel (95%), enzalutamide (25%), cabazitaxel (24%), abiraterone (12%), lutetium-177-prostate-specific membrane antigen (4%), and sipuleucel-T (1%). During/up to 30 days after taxane therapy, 15 pts (8%) had grade 3/4 hematologic adverse events: anemia (erythropenia) (n = 11, 6%), neutropenia (n = 3, 2%), and thrombocytopenia (n = 2, 1%). Median OS was 24.3 (95% CI: 20.9–27.5) months from Ra-223 initiation and 11.8 (95% CI: 10.6–14.1) months from subsequent taxane initiation. Conclusions: In this cohort where Ra-223 was integrated prior to taxane therapy, most pts received multiple subsequent anticancer therapies. It appears that sequencing of multiple treatment modalities with different mechanisms of action may contribute to improved OS. Taxane therapy in routine clinical practice in pts previously treated with Ra-223 had acceptable hematologic safety/tolerability profiles. Clinical trial information: NCT02141438 . [Table: see text]

Purpose: Although high-level evidence supports moderately hypofractionated radiation therapy for definitive prostate treatment, there is less evidence for its use in the postprostatectomy setting. We externally validated a contemporary nomogram predicting biochemical failure (BF) after salvage radiation therapy (SRT) and report long-term disease control outcomes for hypofractionated SRT to the prostate bed. Methods and Materials: A retrospective review was performed for 112 patients treated with hypofractionated SRT (52.5 Gy in 20 fractions using 3-dimensional conformal radiation therapy) for pT2-4R0-1N0/XM0 prostate adenocarcinoma, with postoperative prostate-specific antigen (PSA) greater than 0.1 ng/mL or rising. Freedom from BF (FFBF), distant metastasis, cancer-specific mortality, and overall survival were analyzed from commencement of radiation therapy. Cox regression was performed on FFBF to account for covariates. BF was defined as a PSA >= 0.4 ng/mL and rising after SRT. Early SRT was defined as SRT commencing at a pre-SRT PSA of <= 0.2 ng/mL. Results: Median follow-up was 10.0 years (interquartile range, 9.3-10.7 years), median pre-SRT PSA was 0.4 ng/mL, and androgen deprivation therapy was used in 14% of patients. The 5/10-year FFBF, distant metastasis, cancer-specific mortality, and overall survival were 68%/51%, 7%/16%, 5%/11%, and 90%/75%, respectively. FFBF for early SRT compared with late SRT was 81% versus 66% at 5 years and 68% versus 49% at 10 years. On multivariable analysis, pre-SRT PSA, International Society of Urologic Pathology grade group, seminal vesicle invasion, and androgen deprivation therapy use were associated with FFBF. The nomogram c-index was 0.67, and it overestimated FFBF by 10% and 15% at 5 and 10 years, respectively, with confidence intervals overlapping the line of unity. Conclusions: Hypofractionated SRT provides long-term disease control outcomes comparable to conventionally fractionated radiation therapy. Early SRT provides improved disease control, with two-thirds of patients with pre-SRT PSA of <= 0.2 ng/mL free of BF at 10 years. We performed the first external validation of the Tendulkar salvage nomogram, which showed a robust model performance. (C) 2020 Elsevier Inc. All rights reserved.

Poster: 2019 ASM / R-0109 / Ten year outcomes of hypofractionated salvage post prostatectomy radiotherapy by: S. Chin , A. Fatimilehin, R. Walshaw, H. Mistry, T. Elliot, J. Logue, J. Wylie, A. Choudhury; Manchester/UK

Purpose: To investigate the effectiveness of palliative pelvic radiation therapy (PRT) in patients with bladder cancer and identify factors associated with treatment outcome. Methods and Materials: Patients with bladder cancer receiving PRT were identified retrospectively from 2 cancer centers between 2014 and 2017. Patients were stratified by age, stage, performance status, comorbidities, previous chemotherapy, previous radiation therapy, and radiation therapy protocol. Patients were followed up at 6 weeks after radiation therapy (RT). Median overall survival (mOS) from the last fraction of RT was calculated. Death within 30 days of RT or noncompletion of treatment were considered as futile treatment. Results: Two hundred forty-one patients were identified as receiving PRT. Avariety of RT protocols were used: 8 Gy in 1 fraction (11%), 21 Gy in 3 fractions (15%), 20 Gy in 5 fractions (18%), 36 Gy in 6 fractions (36%), and 27.5 to 30 Gy in 8 to 10 fractions (18%). Thirty-eight percent of patients were of poor performance status (Eastern Cooperative Oncology Group performance status >= 3), and 46.5% had significant comorbidities (Adult Comorbidity Evaluation-27 >= 2). The mOS from the last fraction of RT was 153 days (0-1289 days). The 30-day mortality after radiation therapy was 18% (n = 44), and the rate of incomplete planned radiation therapy treatment was 14% (n = 33). First follow-up information was available in 62% (n = 150) of patients. Median time to this follow-up was 49 days (14-238 days). At first follow-up at about 6 weeks after the last fraction of radiation therapy, symptoms were reported in 150 of 200 (75%) living patients; 80 of 150 (53%) patients reported improvement in symptoms after treatment. There were significant differences in mOS with stage, performance status, and comorbidities. Conclusions: One in 4 patients either did not complete the planned RT course or died within 30 days of treatment. These patients were unlikely to have received maximal benefit from treatment but may have experienced side effects, making treatment futile. Patients with good performance status and earlier stage disease survived longer. Patient selection and comprehensive assessment are crucial in selecting appropriate patients for treatment. (C) 2019 Elsevier Inc. All rights reserved.

We have performed a quality of life (QOL) substudy investigating change in patient reported outcomes (PROs) up to 5 years in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. A total of 3213 men with localized prostate cancer were randomly assigned (1:1:1) to receive 74Gy in 37 fractions, 60Gy in 20 fractions or 57Gy in 19 fractions. A total of 2100 patients were recruited into the QOL substudy. UCLA Prostate Cancer Index (UCLA-PCI), Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline and multiple time points up to 5 years post-radiotherapy. Analysis was on an intention-to-treat basis. Odds of change in symptoms (post-radiotherapy score at each time point minus baseline score) were compared between treatment arms using ordinal logistic regression; analysis of covariance was used to assess change over time for the domain scores, adjusting for baseline/pre-radiotherapy score. A total of 1138 (73%) of the expected 1557 forms were available at 5 years: 352 for 74Gy, 386 for 60Gy and 400 for 57Gy. There was no significant difference in the prevalence or cumulative incidence of patients with overall “moderate or big” bowel, urinary or sexual bother at 5-years between the three arms. There was no significant difference in the odds of "increase in score" from baseline to 5-years for overall bowel or urinary bother between the three arms (Table), and no evidence of an increase in bowel or urinary symptoms from 2 to 5-years. There was some evidence of a larger deterioration in overall sexual function in the 74 Gy arm compared to both hypofractionated arms, which was most marked for sexual bother (Table). Sexual function appeared to deteriorate across all arms between 2 and 5-years. There were no significant differences in general QOL domain scores between arms at 2 and 5 years. Change in bowel or urinary symptoms up to 5 years was similar between the treatment schedules in the CHHiP trial, but there was evidence of less decline in sexual function for the hypofractionated arms compared with the control arm. This supports the use of moderately hypofractionated radiotherapy for localized prostate cancer.Abstract 2; TableOrdinal logistic regression to show odds of "increase in score" from baseline to 5 years for each paired comparison of treatment groupsItemComparisonOdds ratio (99% CI)P-ValueOverall bowel bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy0.78 (0.52, 1.18) 0.75 (0.50, 1.12) 0.96 (0.64, 1.44)0.12 0.06 0.80Overall urinary bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy1.00 (0.67, 1.50) 1.08 (0.72, 1.61) 1.09 (0.73, 1.62)>0.99 0.62 0.58Overall sexual bother60 Gy vs 74 Gy 57 Gy vs 74 Gy 57 Gy vs 60 Gy0.55 (0.30, 0.99) 0.52 (0.29, 0.94) 0.95 (0.53, 1.70)0.009 0.004 0.82 Open table in a new tab

Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns. (C) 2017 European Association of Urology. Published by Elsevier B.V.