Anatomical patterns of recurrence following biochemical relapse after post‐prostatectomy salvage radiation therapy: a multi‐institutional study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/1/bju13792.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/2/bju13792_am.pd

Body composition and mortality in men receiving prostate radiotherapy: A pooled analysis of NRG/RTOG 9406 and NRG/RTOG 0126

PurposeTo validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality.Materials and MethodsParticipants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4–L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death.ResultsData from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area.ConclusionsThis study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.This study strongly supports that body composition is related to mortality in men with localized prostate cancer. The inclusion of psoas area in the recursive partitioning analysis classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175907/1/cncr34596_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175907/2/cncr34596.pd

Association of black race with improved outcomes following definitive radiotherapy with androgen deprivation therapy for high-risk prostate cancer: A meta-analysis of eight randomized trials

327 Background: Though Black men with prostate cancer are more likely to have aggressive disease features than White men, race-specific differences in initial treatment responses in localized disease remains unknown. Methods: Individual patient data were obtained for 9259 patients (including 1674 [18.1%] Black men and 7585 [81.9%] White men) enrolled on eight randomized controlled trials evaluating definitive radiotherapy (RT) ± short-term or long-term androgen deprivation therapy (STADT and LTADT). The primary endpoints were biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Fine-Gray subdistribution HR (sHR) models were developed to evaluate the cumulative incidences of all endpoints after stratification by National Comprehensive Cancer Network risk grouping. A meta-analysis was done to estimate pair-wise comparisons of treatments within and between Black and White men, after adjusting for age, Gleason score, clinical T stage, and initial PSA. Results: Black men were more likely to have NCCN high-risk disease at enrollment (656/1674 [39.2%] vs 2506/7585 [33%], p<0.001). However, within the high-risk stratum Black men had lower 10-year rates of BCR (46.1% vs. 50.4%, p=0.02), DM (14% vs. 21.6%, p<0.001), and PCSM (4.9% vs. 9.8%, p<0.001). After adjusting for age and disease characteristics, Black men with high-risk prostate receiving RT+STADT had lower rates of BCR (sHR 0.73, 95% CI 0.62-0.86, p<0.001), DM (sHR 0.64, 95% CI 0.49-0.84, p=0.001) and PCSM (sHR 0.49, 95% CI 0.25-0.95, p=0.04). There were no differences in BCR, DM, or PCSM among men receiving RT+LTADT. The interaction between race and the impact of adding STADT to RT alone on BCR was statistically significant (p=0.003). Conclusions: Black men enrolled on randomized trials with long-term follow-up have higher risk disease at enrollment, but have better BCR, DM, and PCSM outcomes with RT-based therapy compared with White men, particularly with the addition of STADT

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R was 0·7 or greater. 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R 0·28 [0·0045-0·65]), and local failure (R 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R 0·78 [0·59-0·89]) correlated strongly. Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. Prostate Cancer Foundation and National Institutes of Health

Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis.

PurposeThere remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.MethodsMEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).ResultsThe median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups.ConclusionThe sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity

Up-grading and performance: the role of design, technology and business strategy in Hong Kong's electronics industry

Hong Kong, Competitiveness, Business Strategy, Capabilities, Performance,

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials

In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise