scholarly journals 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 33 (19) ◽  
pp. 2143-2150 ◽  
Author(s):  
Malcolm D. Mason ◽  
Wendy R. Parulekar ◽  
Matthew R. Sydes ◽  
Michael Brundage ◽  
Peter Kirkbride ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Final Report ◽  
Locally Advanced Prostate Cancer

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.

Ten-Year Follow-Up of Radiation Therapy Oncology Group Protocol 92-02: A Phase III Trial of the Duration of Elective Androgen Deprivation in Locally Advanced Prostate Cancer

2008 ◽  
Vol 26 (15) ◽  
pp. 2497-2504 ◽  
Author(s):  
Eric M. Horwitz ◽  
Kyounghwa Bae ◽  
Gerald E. Hanks ◽  
Arthur Porter ◽  
David J. Grignon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Gleason Score ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
End Points

PurposeTo determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT).Patients and MethodsProstate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms.ResultsAt 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P ≤ .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein.ConclusionLTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.

scholarly journals The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
Curative Intent ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

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.

Recent Developments in Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

2014 ◽  
Vol 10 (02) ◽  
pp. 133
Author(s):  
David A Bader ◽  
Jasmina Z Cerne ◽  
Sean E McGuire ◽  
◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Second Generation ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
External Beam Radiation ◽  
Locally Advanced Prostate Cancer ◽  
Recent Developments

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.

Intergroup randomized phase III study of androgen deprivation therapy (ADT) plus radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT: T94-0110; NCT00002633).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA4504-CRA4504 ◽  
Author(s):  
P. R. Warde ◽  
M. D. Mason ◽  
M. R. Sydes ◽  
M. K. Gospodarowicz ◽  
G. P. Swanson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Disease Specific Survival ◽  
Locally Advanced Prostate Cancer ◽  
Combined Modality ◽  
Disease Specific

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA > 40 μ g/l (119) or T2 PSA > 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.

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