Androgen Suppression and Radiation vs Radiation Alone for Prostate Cancer

Abstract

EVERAL RANDOMIZED STUDIES [1][2][3][4][5] have documented a prolongation in overall survival, prostate cancer-specific survival, or both when androgen suppression therapy (AST) is combined with external beam radiation therapy (RT) compared with RT alone in the management of unfavorable localized and locally advanced prostate cancer. Therefore, in men with these stages of disease, RT and AST have become a standard of care.However, evidence from pooled analyses of randomized studies 6 as well as large patient cohort studies 7,8 suggests that AST administration is associated with an increased risk of fatal 6 and nonfatal 7,8 cardiovascular events in men of advanced age. A possible explanation for this association is that as men age, they often acquire comorbid illnesses and these comorbidities may increase the negative effects of specific anticancer treatments such as AST. As a result, it is possible that the survival benefit observed when AST is added to RT may vary among specific subsets of patients defined by their comorbid illness profile.In this study, we first report the results of the long-term follow-up of a randomized study of 6 months of AST and RT vs RT alone. The results of shorterterm follow-up, ie, at 4.5 years, have been previously reported. 5 In addition, we performed an analysis of overall survival in subgroups defined by their level of comorbidity at the time of randomization and evaluated whether an interaction existed between the level of comorbidity and treatment group with respect to time to all-cause mortality. METHODSPatient Population and Treatment At academic (Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center) and community-based (St Anne's Hospital, Metrowest Medical Center, and Suburban Oncology Center) medical centers in Massachusetts,

Definitive radiotherapy with adjuvant long-term antiandrogen treatment for locally advanced prostate cancer: health-related quality of life and hormonal changes

“…It has recently been shown in a randomized trial that even though complete androgen blockade adjuvant to RT compared with RT alone resulted in a mortality benefit, this was not true for subgroups with moderate or severe comorbidity. 33 Such identification of patients for whom side effects from adjuvant treatment outweigh the antitumour effects is important in order to individualize therapy. In our opinion, precautions should be made until the possible relation between AAs and cardiovascular morbidity is clarified.…”

Advances and future directions in management of prostate cancer

“…Therefore, only in select cases ADT is given as primary treatment for localised prostate cancer. In conjunction with external beam radiation therapy, 2 years of androgen deprivation is clearly advantageous [11]. In patients with positive lymph nodes following radical prostatectomy, addition of androgen deprivation improves survival [12].…”

Mortality in men with localized prostate cancer treated with brachytherapy with or without neoadjuvant hormone therapy

“…Because an increase in ACM was noted only for men aged >73 years, in whom increased comorbid illness would be expected compared with men aged <73 years, it is likely that the interaction noted in a postrandomization analysis between ADT and the Adult Comorbidity Evaluation-27 comorbidity score, in which men with moderate to severe comorbidity did not benefit in terms of overall survival for the addition of ADT to radiotherapy, also may explain the current results. 13 Specifically, ADT may accentuate underlying comorbidity, which probably is cardiovascular based on previous reports. [2][3][4]13 Finally, prior randomized studies have demonstrated an overall and/or cancer-specific survival benefit with the addition of hormone therapy to external-beam radiation in men with high-risk disease.…”

“…13 Specifically, ADT may accentuate underlying comorbidity, which probably is cardiovascular based on previous reports. [2][3][4]13 Finally, prior randomized studies have demonstrated an overall and/or cancer-specific survival benefit with the addition of hormone therapy to external-beam radiation in men with high-risk disease. [13][14][15][16][17] In the current study, 12% of patients had high-risk disease; however, hormone therapy was used in conjunction with brachytherapy, and a survival benefit has not been demonstrated with the addition of hormone therapy in that setting.…”

“…[2][3][4]13 Finally, prior randomized studies have demonstrated an overall and/or cancer-specific survival benefit with the addition of hormone therapy to external-beam radiation in men with high-risk disease. [13][14][15][16][17] In the current study, 12% of patients had high-risk disease; however, hormone therapy was used in conjunction with brachytherapy, and a survival benefit has not been demonstrated with the addition of hormone therapy in that setting. 18 Therefore, because there may be a detriment to ADT use in older men, as suggested by the current results, and because the men who were selected for treatment who had high-risk disease represented the community-based practice for implantation monotherapy with or without hormone therapy, we believe that their inclusion was important.…”