PURPOSE:Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS:Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS:Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). CONCLUSION:White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

310 Background: To determine the potential impact of persistent hypogonadism on overall survival (OS) after prolonged androgen deprivation therapy (ADT) in patients (pts) with high-risk prostate cancer. Methods: From 10/2000 to 01/2008, 630 pts were randomised to pelvic radiotherapy (RT) plus 36 (310 pts) vs. 18 months (320 pts) of ADT. Serum testosterone (T) was prospectively collected at baseline, then regularly. We defined T recovery as a return of T to within the normal range value of each participating institution, regardless of whether it was initially normal or abnormal. Excluded from the analysis were pts not receiving exactly 18 or 36 months of ADT (48), or had no T measured at baseline or during follow-up (67). We compared OS between patients recovering or not T to a normal level using the log rank test. Multivariable analysis to predict OS included recovered T to a normal level, age, Zubrod, comorbidities, baseline PSA, Gleason score, stage and ADT duration. Results: 515/630 pts had proper T data available (baseline and follow-up) and were retained for the analysis. The results are reported with a median follow-up of 17.4 years. Over a period of 22 years, 6587 T measurements were available. A total of 270/515 pts (52.4%) recovered T to normal level, 188/330 (57%) in the 18-month and 82/185 (44.3%) in the 36-month cohort, p=0.006. Pts not recovering T to a normal level were older, had higher clinical stage and diabetes. Among pts regaining T to a normal level, the median time to T recovery was 3.6 (IQR 2.9-4.9) years.10- and 15-year OS rates were 76% (71-81) and 44% (38-51) for pts recovering T vs. 55% (49-62) and 30% (24-36) for those who did not, p<0.001. A significant lower risk of death favoured pts recovering T when considering the global hazard ratio (HR) [HR (95% CI) = 0.54 (0.44-0.67), p<0.001]. Significant differences in HR for death are maintained for both 18-month [HR = 0.51 (0.39-0.66), p<0.001] and 36-month cohort [HR = 0.58 (0.40-0.84), p=0.004]. In multivariable analyses, the impact of T recovery remains significant for the risk of death [(HR = 0.69 (0.55-0.86), p=0.001], and also for the 18-month [HR = 0.70 (0.53-0.93), p=0.013] and the 36-month cohort [(HR = 0.61 (0.40-0.93), p=0.021]. In a multivariable model, among pts regaining T to a normal level, the time to T recovery had no impact on OS [HR = 0.97 (0.90-1.04), p=0.41]. Of note, there was no significant difference in the rate of death from prostate cancer between pts recovering or not T (11.9% vs. 13.5%, p=0.58). Competing risk analysis confirms this finding [sHR = 0.83 (0.51-1.35), p=0.57]. Conclusions: In high-risk prostate cancer treated with RT and long-term ADT, T recovery to normal level is associated with a significant improvement in overall survival. The increased death rate in pts not recovering T is likely due to causes unrelated to prostate cancer. Clinical trial information: NCT00223171 .

Background:Symptomatic posttreatment edema (SPTE) is a complication that may develop after radiotherapy for intracranial meningiomas. Our study aims at reviewing rates of SPTE in a large cohort of a single institution and identifying possible predictive factors. Methods:We retrospectively analyzed data of 293 patients with 304 intracranial meningiomas irradiated at our institution between 2005 and 2018. We evaluated rates of SPTE and investigated numerous factors by univariate and multivariate analysis. Kaplan Meier analysis was used for estimation of actuarial local control and overall survival. Results:Median age was 60 years. Meningiomas were treated with fractionated stereotactic radiation therapy (70 %), single fraction stereotactic radiosurgery (24 %) or fractionated stereotactic radiosurgery (6 %). Median imaging follow-up was 60 months, actuarial 10 year local control rate for patients with grade 1 meningiomas who received radiotherapy as definitive treatment was 99 %. Local control at 5 years was 94 % for grade 1 meningioma, 57 % and 53 % for grade 2 and 3 respectively. Sixteen patients (5.5 %) developed SPTE, median time to onset was 3 months (range 1-26 months). the higher rates of SPTE observed were in midline (13 %) and convexity (9 %), compared to skull base tumors (2 %). On univariate analysis, age > 60 years (p > 0.03), pretreatment peritumoral edema (p = 0.014), medline location (p = 0.018), tumor size > 30 mm (p = 0.015) and grade 2 histology (p = 0.03) were predictive of SPTE. On multivariate analysis, only tumor location and size remained statistically significant. Conclusions:Based on our results, patients at high risk of SPTE can be identified based on patient and tumor characteristics. The best treatment technique in high risk patients is yet to be defined.

Standard systemic treatment has not been established for refractory meningioma. This retrospective study aimed to identify prognostic factors for overall survival and document outcomes of systemic therapies. We reviewed patients with meningioma followed at CHUM hospital between 2006 and 2022. Only patients with progression after first-line treatment were included. Among 750 patients, 107 (14%) experienced progression after first-line treatment. They were divided into two groups: Group 1 (n = 69, 64%) received salvage local treatments, and Group 2 (n = 38, 36%) received additional salvage systemic treatments. The median follow-up time from diagnosis was 7.5 years. 10-year OS was 88.3% (Group 1) vs. 67.2% (Group 2) (p = 0.009). Mean survival after stopping systemic treatment was 8.94 months. Key prognostic factors for poorer survival included age ≥ 65 (HR = 2.82; p = 0.009), WHO grade 2 or 3 (HR = 4.25; p = 0.004), and progression after second-line treatment (HR = 4.77; p = 0.004). Bevacizumab was associated with a mPFS of 12 months and 1-year OS of 64,6%, whereas non-Bevacizumab treatments—including Hydroxyurea, Somatostatin, and Sunitinib—were associated with a mPFS of 7 months and 1-year OS of 52,6%. This study highlights the fatal nature of recurrent meningiomas and the urgent need for systemic treatments that can improve their survival.

BACKGROUND AND OBJECTIVE:The PROFIT trial was designed to compare moderately hypofractionated (HF) radiotherapy versus conventional fractionation (CF) for patients with intermediate-risk prostate cancer (IR-PC). Similar efficacy and toxicity outcomes were previously reported. The aim of the current analysis was to evaluate differences in long-term patient-reported outcomes (PROs) between the HF and CF arms in PROFIT. METHODS:For the PROFIT phase 3 randomized clinical trial, patients with IR-PC (n = 1206) were enrolled from 14 sites in Canada, 12 in Australia, and one in France and randomized to receive 78 Gy in 39 fractions over 8 wk (CF) or 60 Gy in 20 fractions over 4 wk (HF). PROs were evaluated at baseline and 24 and 48 mo using the Expanded Prostate Cancer Index Composite, American Urological Association Symptom Score (AUASS), and the 12-item Short Form Health Survey (SF-12) comprising a physical component summary (PCS) and a mental component summary (MCS). A minimally important difference (MID) was defined as a deterioration in domain- or subdomain-specific health-related quality of life (HRQoL) score by ≥0.5 times the standard deviation at each time point in comparison to baseline. Statistical significance was set at p < 0.01. KEY FINDINGS AND LIMITATIONS:AUASS results were similar and stable over time in both arms (median 5 points, interquartile range 2-9; p > 0.2). There were no significant differences in scores for urinary, bowel, sexual, and hormonal domains or subdomains between the arms at any time point (p > 0.02). The greatest decline over time occurred in sexual domain, with a decrease of ≥10 points from baseline to 24 mo in both arms. SF-12 mean scores for both PSC and MSC were similar in the two arms and remained stable at all time points. The only significant differences in the proportion of patients reporting MIDs were for the bowel subdomains at 48 mo, with significant MID reductions favoring HF for both the bowel summary score (53% vs 44%; p = 0.01) and bowel function score (51% vs 39%; p = 0.001). Overall treatment satisfaction was high in both arms: ≥88% of patients were either satisfied or extremely satisfied with their treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS:PRO results from the PROFIT trial suggest no significant differences in urinary, bowel, sexual, hormonal, and general HRQoL between CF and HF radiotherapy schedules. This study provides level 1 evidence supporting the use of moderate HF radiotherapy as standard treatment in patients with IR-PC. This trial is registered on ClinicalTrials.gov as NCT00304759.

BACKGROUND:We aim to evaluate whether increased lymph node yield at prostatectomy (RP) is associated with improved outcomes in NRG/RTOG 9601, a randomized clinical trial of men who underwent either radiation (RT) alone or RT + bicalutamide for PSA elevation following RP for pT2/T3 prostate cancer. METHODS:We reviewed available pathology reports for patients in NRG/RTOG 9601 to determine the nodal count at RP. Cox proportional hazards models were used to assess effect of lymph nodes yield, arm (RT alone or RT + bicalutamide), Gleason score, positive margins, and seminal vesicle invasion on the following endpoints: times to local and distant failure and overall and disease-specific survival. RESULTS:Of 760 patients, 552 (73%, 276 in each arm) had complete data available. Median node count in the entire cohort was 6 (range: 0-33, IQR: 3-9). There were no significant differences between arms in terms of patient demographic or clinical characteristics, including total lymph nodes removed in either arm. There was no significant association between total lymph nodes and overall or disease-specific survival with both arms combined and when adjusting for arm. Notably, interaction analysis revealed that in seminal vesicle invasion, there was a significant association between lymph node yield and OS and DSS (HR = 0.91, 95% CI: 0.83-0.99, p = 0.034; HR = 0.87, 95% CI: 0.77-0.99, p = 0.029, respectively). CONCLUSIONS:Although lymph node yield in NRG/RTOG 9601 did not show association with adverse outcomes in the entire cohort or either arm alone, there was significant association between lymph node yield and adverse outcomes when seminal vesicle invasion was present. The therapeutic benefit of extensive lymph node dissection remains uncertain but could be more relevant in higher risk patients.

BACKGROUND:The outcomes of radiosurgery for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) are not as extensively assessed as those for idiopathic or classical TN cases. OBJECTIVE:Evaluate the safety and efficacy of radiosurgery for TN in MS patients and identify potential predictors of successful outcomes. METHODS:A retrospective single-institution cohort study with patients treated between 2009 and 2022 was performed. Fifty patients were included, and a total of 68 radiosurgical interventions were delivered. Outcomes included the maintenance of pain relief assessed using Kaplan-Meier curves and treatment-related complications. Cox regression analyses were used to identify potential predictors of better pain relief. RESULTS:Following the first radiosurgical treatments, the initial pain relief rate was 86% after a median latency period of 14 days. Adequate pain relief rates at 6, 12, 36 and 60 months were 86%, 52%, 35% and 24%, respectively. Adequate pain relief was sustained for an actuarial median of 12.7 months. After initial relief, pain recurrence occurred in 68% of patients. No statistical difference was seen in the duration of pain relief after initial or repeat radiosurgery (p = 0.368). The most frequent complication was facial hypesthesia (Barrow Neurological Institute facial hypesthesia scale grade II: 10%; III: 6%; IV: 0%). Ipsilateral vascular compression was predictive of better efficacy (p = 0.024). CONCLUSION:Radiosurgery for TN in patients with MS appears to be safe and to provide effective pain relief. Notably, radiological identification of vascular compression may predict more sustained pain relief.

BACKGROUND AND OBJECTIVE:Biochemical recurrence (BCR) after radical prostatectomy (RP) is a heterogeneous disease state in prostate cancer with multiple treatment options. Improved risk stratification could enable more personalized decision-making. We developed and validated a digital pathology-based multimodal artificial intelligence (MMAI) model to predict outcomes in post-RP BCR patients undergoing salvage therapy. METHODS:An MMAI model was trained to predict distant metastasis (DM) using prostate histopathology image features and clinical variables (pathologic grade group, pathologic T stage, prostate-specific antigen level before salvage radiotherapy [SRT], age, and surgical margin). The locked model was validated in 533 patients from NRG/RTOG 9601 and 0534 treated with SRT ± hormone therapy (HT), using Cox regression and time-dependent area under the receiver operating characteristic curve. KEY FINDINGS AND LIMITATIONS:With a median follow-up of 9.3 yrs, MMAI score was significantly associated with DM (subdistribution hazard ratio = 2.17 per standard deviation [95% confidence interval 1.65-2.85]; p < 0.001) and remained independently prognostic after adjusting for clinical variables and treatment. The 10-yr time-dependent area under the receiver operating characteristic curve for MMAI was 0.74 compared with 0.68 for a clinical nomogram. Binary risk categorization demonstrated higher 10-yr DM incidence in the MMAI high-risk (25%) than in the low-risk (8.8%) group. The absolute reduction in 10-yr DM incidence with HT plus SRT versus SRT alone was 21% in the high-risk group versus 2.5% in the low-risk group. Limitations include the use of archived trial cohorts. CONCLUSIONS AND CLINICAL IMPLICATIONS:The post-RP MMAI model provides individualized risk estimates after SRT ± HT and may support shared decision-making about salvage treatment. External and prospective validation are ongoing.

PURPOSE:There is a need to better understand the molecular features that characterize grade 3 astrocytomas and their significance in predicting clinical outcomes. The aim of this study was to determine the significance of the 2021 World Health Organization (WHO)-defined molecular subgroups, along with MGMT promoter methylation, and other alterations in NRG Oncology/RTOG 9813. METHODS AND MATERIALS:Mutation status was determined by immunohistochemistry and/or next-generation sequencing. Copy number alterations and MGMT methylation were determined by Affymetrix Oncoscan and/or Illumina 450K arrays. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and tested using the log-rank test. Multivariable analyses used Cox proportional hazards models. RESULTS:Application of the 2021 WHO-defined criteria resulted in the reclassification of 26/79 (33%) patients to grade 4 astrocytoma, IDH-mutant or glioblastoma. When looking at newly assigned molecular grade, grade 3 patients experienced longer survival outcomes compared to grade 4 patients. As individual biomarkers, IDH1/2 mutations, MGMT promoter methylation, and ATRX mutations were each associated with longer survival, whereas TERT promoter mutations, EGFR amplification, and gain of chromosome 7/loss of 10 (Chr+7/-10) were associated with shorter survival. Similar survival outcomes were observed for MGMT methylated patients treated with radiation therapy (RT) and temozolomide (TMZ) or RT and BCNU/CCNU, and MGMT unmethylated patients treated with RT and TMZ. Additionally, IDH-mutant patients seemed to respond well to the addition of TMZ. CONCLUSIONS:This study demonstrated the importance of classifying patients according to the 2021 WHO-defined criteria. The majority of IDH-wildtype anaplastic astrocytomas (grade 3) were reclassified as glioblastoma (grade 4). These analyses also shed light on the efficacy of TMZ in certain molecular subgroups, where the addition of TMZ to RT appeared to benefit patients regardless of MGMT methylation status.

PURPOSE:Salvage radiation therapy (RT) is used in men with prostate cancer (PC) recurrence following radical prostatectomy signaled by a persistent or delayed elevation in prostate specific antigen. It was previously reported that the use of antiandrogen therapy (AAT) with RT improved cancer control and overall survival (OS). Long-term follow-up results are presented in this study. METHODS AND MATERIALS:From 1998 to 2003, 760 eligible postradical prostatectomy patients with stage pT3N0 or with pT2N0 and positive margins and prostate specific antigen from 0.2 to 4.0 ng/mL were randomly assigned on a double-blinded, placebo-controlled trial of RT + placebo versus RT + AAT (24 months of bicalutamide, 150 mg daily) during and after RT (64.8 Gy in 36 fractions prostate bed). The primary endpoint was OS estimated using Kaplan-Meier method. Time to PC death and metastatic PC (competing risk of death without an event) was estimated using cumulative incidence. The hazard ratio (HR) was obtained using Cox models (OS) and subdistribution HRs (sHRs) used the Fine-Gray model (time to PC death and metastatic PC). RESULTS:Median follow-up for surviving patients was 18.9 years. OS at 18 years was 53% (95% CI, 47%-58%) for RT + AAT and 43% (95% CI, 38%-49%) for RT + placebo (adjusted HR = 0.82; 95% CI, 0.67-1.00; 1-sided P = .025). The 18-year incidence of centrally reviewed PC deaths was 18% (95% CI, 14%-22%) RT + AAT and 28% (95% CI, 23-33%) RT + placebo (unadjusted sHR = 0.63; 95% CI, 0.46-0.84; 2-sided P = .002). The 18-year incidence of metastatic PC was 22% (95% CI, 18-26%) and 31% (95% CI, 26-36%) for AAT and placebo arms, respectively (unadjusted sHR = 0.62; 95% CI, 0.46-0.83; 2-sided P = .001). CONCLUSIONS:Long-term results of 24-month duration AAT during and after salvage RT are consistent with the primary report with significantly improved long-term OS, reduced incidence of metastatic PC, and PC death for RT + AAT. In comparison with previous reports, the improvement in OS with AAT has risen from 5% at 12 years to 9.8% at 18 years.

PURPOSE Artificial intelligence (AI) tools could improve clinical decision making or exacerbate inequities because of bias. African American (AA) men reportedly have a worse prognosis for prostate cancer (PCa) and are underrepresented in the development genomic biomarkers. We assess the generalizability of tools developed using a multimodal AI (MMAI) deep learning system using digital histopathology and clinical data from NRG/Radiation Therapy Oncology Group PCa trials across racial subgroups. METHODS In total, 5,708 patients from five randomized phase III trials were included. Two MMAI algorithms were evaluated: (1) the distant metastasis (DM) MMAI model optimized to predict risk of DM, and (2) the PCa-specific mortality (PCSM) MMAI model optimized to focus on prediction death in the presence of DM (DDM). The prognostic performance of the MMAI algorithms was evaluated in AA and non-AA subgroups using time to DM (primary end point) and time to DDM (secondary end point). Exploratory end points included time to biochemical failure and overall survival with Fine-Gray or Cox proportional hazards models. Cumulative incidence estimates were computed for time-to-event end points and compared using Gray's test. RESULTS There were 948 (16.6%) AA patients, 4,731 non-AA patients (82.9%), and 29 (0.5%) patients with unknown or missing race status. The DM-MMAI algorithm showed a strong prognostic signal for DM in the AA (subdistribution hazard ratio [sHR], 1.2 [95% CI, 1.0 to 1.3]; P = .007) and non-AA subgroups (sHR, 1.4 [95% CI, 1.3 to 1.5]; P < .001). Similarly, the PCSM-MMAI score showed a strong prognostic signal for DDM in both AA (sHR, 1.3 [95% CI, 1.1 to 1.5]; P = .001) and non-AA subgroups (sHR, 1.5 [95% CI, 1.4 to 1.6]; P < .001), with similar distributions of risk. CONCLUSION Using cooperative group data sets with a racially diverse population, the MMAI algorithm performed well across racial subgroups without evidence of algorithmic bias.

Purpose The impact of persistent hypogonadism post-androgen deprivation therapy (ADT) on overall survival (OS) of patients with prostate cancer (PCa) is poorly documented. We compared OS between patients who recovered testosterone and those who did not after ADT. Methods and Materials Patients with PCa with intermediate- or high-risk disease were treated with ADT for 6, 18, or 36 months plus radiation therapy in 2 randomized trials. We compared OS between patients who recovered testosterone to a normal level to those who did not, using the log rank test. Multivariable Cox analysis to predict OS included recovered testosterone, age, Zubrod performance, comorbidities, baseline prostate specific antigen, Gleason score, stage, and ADT duration. To avoid immortal time bias, we performed a landmark analysis for each cohort. Results The median follow-up was 16.6 years. Patients not recovering testosterone to a normal level were older, with more associated medical comorbidities. All the results are reported respectively for the 6-, 18-, and 36-month ADT cohorts. Testosterone recovery rates, to normal level, were 76.7%, 58.6%, and 45.3% with a median time to testosterone recovery of 1.64, 3, and 5 years, respectively. The 10-year OS rates were significantly higher in patients recovering testosterone: 77% versus 61%, P < .001; 73% versus 51%, P < .001; and 78% versus 62%, P < .001. However, multivariable analyses with landmark time points failed to show testosterone recovery as an independent predictor. The study is limited by its post hoc analysis. Conclusions In patients with PCa, our study shows that persistent hypogonadism post-ADT is associated with worse survival, particularly in older patients with medical conditions.

Purpose/Objective(s) Aiming to confirm that biochemical recurrence (BR) is not a surrogate for overall survival (OS) in patients (pts) treated for intermediate risk prostate cancer (IRPC) and high-risk prostate cancer (HRPC), we analyzed data from our two prospective phase III randomized trials. Materials/Methods From October 2000 to September 2010, 1230 pts were randomized in two phase III trials. 600 pts with IRPC were treated using prostate radiotherapy (RT) alone (200 pts) or with 6 months (m) ADT (400 pts) and 630 pts with HRPC were treated with pelvic + prostate RT and 18 or 36 m ADT. The Chi-squared test compared BR rates between cohorts. The log rank test compared the OS rates between IRPC vs. HRPC pts and in pts with or without BR by considering all follow-up values. OS rates were estimated with Kaplan Meier curve. Results With a median follow up of 16.3 years(y) (interquartile range = 13.0 à 19.5), 722/ 1230 (58.7%) pts had died. Median age at randomization was 71 y and 82 y at death. The 10-y OS rates in IRPC vs HRPC were respectively 73% (69-77) vs. 63% (60-67). HRPC pts died significantly faster than IRPC pts [Hazard Ratio (95% confidence interval) = 1.30 (1.12-1.51), p<0.001]. One hundred fifty-three IRPC pts (25.5%) developed BR at a median time of 6.5 years post-randomization and 89 of 153 had died. Forty-seven pts (7.8%) presented BR in the first 5 years post-randomization, 84 (14%) between 6 and 10 y and 22 (3.7%) after 10 y. The rate of BR was significantly higher in pts not receiving ADT: 79/202 (39.1%) vs 74/398 (18.6%), p<0.001. 447/600 (74.5%) pts were free from BR at a median FU of 13.4 years. 49 IRPC pts (8.2%) died in the first 5 y post-randomization, 112 (19%) between 6 and 10 y and 144 (24%) after 10 y. There was no significant difference in OS between pts with vs without BR [10-y OS: 79% (73-86) vs 71% (67-75), (95% CI) = 0.93 (0.72-1.19), p = 0.5]. 197 HRPC pts (31.3%) developed BR at a median time of 5.9 y post-randomization (IQR = 3.5-7.9) and 139/197 had died. 91 pts (15.2%) presented BR in the first 5 years post-randomization, 80 (13.3%) between 5 and 10 y, and 26 (4.3%) after 10 y. The rate of BR was significantly lower in pts receiving 36 vs 18 m: 85/310 (27.4%) vs. 112/320 (35.0%), p = 0.048. 433/630 (68.7%) pts were free from BR at a median FU of 15.9 y (IQR 12.9-18.7). 72 HRPC pts (12%) died in the first 5 y post-randomization, 155 (26%) between 6 and 10 y and 190 (32%) after 10 y. There was no significant difference in OS between pts with vs without BR [10-y OS: 63% (57-70) vs. 63% (59-68), HR (95% CI) = 0.92 (0.75-1.13), p = 0.4]. Conclusion Based on the long-term follow up of 1230 pts with localized PC, we confirm that BR is not a surrogate for OS in IRPC or HRPC.

Background: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. Objective: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. Design, setting, and participants: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. Intervention: Short-term ADT. Outcome measurements and statistical analysis: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate -specific antigen (PSA), to stratify patients according to relative hazards for primary cancer -related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score.

296 Background: In prostate cancer (PCa) treated with androgen deprivation therapy (ADT) and radiotherapy (RT), limited prospective data exist regarding weight variation during ADT. Using our prospective data from two phase III trials we compare the magnitude of weight variation during different duration of ADT. Methods: 400 patients (pts) with intermediate risk PCa received 6 months of ADT (Bicalutamide 1 month (m) and Goserelin 10,8 mg x 2), and 630 pts with high-risk PCa were treated with 18 or 36m of ADT (Bicalutamide 1m and Goserelin 10,8 mg x 6 or 12). Pts’ weights were measured at baseline then at each Goserelin dose. 463/1030 pts were excluded from the analysis: 90 no or incomplete ADT, 127 no initial weight and 246 no weight at the end of ADT. Regular patient weighing was available in 567/1030 pts (55%) from whom 250, 191 and 124 received, respectively, 6, 18 or 36m of ADT. Pt’s characteristics and weights were compared with Kruskal-Wallis and Chi squared test between groups of ADT. Multivariable logistic regression was performed to assess predictors of weight gain over 2 kg. Variables included were duration of ADT, age ≥65 vs. < 65 and baseline comorbidities (cardiovascular disease, diabetes, chronic obstructive pulmonary disease, hypertension). Results: Comparing weights between the beginning and the end of ADT, 375/567 (66.1%) pts gained and 192/567 (33.9%) lost weight. The mean ± SD weight gain at the end of ADT was significantly higher in pts receiving 18m of ADT (1.98 ± 4.05) or 36m (2.38 ± 5.15) compared to pts receiving only 6m (0.98 ± 3.10, p=0.003). As ADT duration increased (6, 18 or 36m), weight gain over 2 kg (34.1% vs. 48.2% vs. 53.2%, p<0.001) and over 4 kg (12.7% vs. 26.2% vs. 36.3%, p<0.001) significantly increased. In multivariable logistic regression, predictors of weight gain over 2 kg were 18m ADT [OR=1.85 (1.25-2.74), p=0.002] and 36m ADT [OR=2.23 (1.43-3.48), p<0.001] compared to 6m ADT and non-diabetic pts (OR=2.13 (1.28-3.54), p=0.003). Age was not a factor. In the 375 pts who gained weight, the rate of patients that gained 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (47.2%, 33.1% and 19.6%) in the 163 receiving 6m ADT, (30.3%, 32.6% and 37.1%) in 132 pts receiving 18m ADT, and (17.6%, 26.3% and 56.4%) in the 80 pts receiving 36m ADT. In the 192 pts who lost weight, the rate of patients that lost 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (62.9%, 21.3% and 15.6%) in 89 receiving 6m ADT, (50.8%, 27.1% and 22.1%) in 59 pts receiving 18m ADT and (59.1%, 15.9% and 25%) in 44 pts receiving 36m ADT. Conclusions: ADT is not associated with weight gain in all pts. Based on our prospective data, one third of pts lose weight at the end of ADT. However, weight gain above 2 kg or 4 kg increases with ADT duration and non-diabetics pts, regardless of age. Weight monitoring in pts receiving ADT should be done regularly and pts counseled accordingly.