scholarly journals Re: Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

2015 ◽  
Vol 2 (2) ◽  
pp. 107-107
Author(s):  
Tayyar Alp Özkan
2015 ◽  
Vol 33 (19) ◽  
pp. 2143-2150 ◽  
Author(s):  
Malcolm D. Mason ◽  
Wendy R. Parulekar ◽  
Matthew R. Sydes ◽  
Michael Brundage ◽  
Peter Kirkbride ◽  
...  

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.


2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario

Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.


2014 ◽  
Vol 10 (02) ◽  
pp. 133
Author(s):  
David A Bader ◽  
Jasmina Z Cerne ◽  
Sean E McGuire ◽  
◽  
◽  
...  

Locally advanced prostate cancer (LAPC) is often managed with a combination of external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). Clinical protocols combining ADT and EBRT for the treatment of LAPC were developed based on clinical trials that used conventional-dose EBRT (~70 Gy) and luteinizing hormone-releasing hormone (LHRH) analog monotherapy. However, dose-escalated EBRT (>74 Gy) is in widespread clinical use and potent second-generation agents targeting the androgen axis have recently received US Food and Drug Administration (FDA) approval. These and other recent developments challenge the current standard of care for LAPC. Determining the optimal duration and potency of ADT in combination with dose-escalated EBRT in LAPC is an active area of clinical research seeking to balance the side-effect profile of ADT with its well-established therapeutic benefits. Prospective randomized clinical trials incorporating dose-escalated EBRT and second-generation androgen axis inhibitors are necessary to clarify the role of ADT in this new arena. Further, since biochemical response to neoadjuvant ADT predicts for efficacy of EBRT, new trials should seek to achieve maximal androgen suppression prior to EBRT to increase clinical benefit. Last, recent clinical and preclinical research efforts hold significant promise and seek to provide better predictive markers and expand the therapeutic target spectrum in prostate cancer.


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