Due to the lack of evidence indicating a significant oncologic benefit to treatment with primary ADT for clinically localized prostate cancer, the Panel concluded primary ADT should only be recommended for palliation of local disease-related symptoms in select patients with a limited life expectancy for whom definitive local therapy is not advised. Indeed, among eight cohort studies evaluating survival outcomes between primary ADT and observation in prostate cancer populations of various risk categories - all of which were rated as having a moderate risk of bias - none demonstrated improvements in all-cause or prostate cancer-specific survival.39, 155-161 Moreover, in a cohort study of patients with unfavorable intermediate- or high-risk clinically localized prostate cancer, no significant differences were identified between immediate treatment with primary ADT versus observation with regard to all-cause (adjusted HR: 0.69; 95% CI: 0.45 to 1.07) or prostate cancer-specific mortality (adjusted HR: 2.69; 95% CI: 0.77 to 9.32).155 Likewise, in a population-based analysis of patients with poorly differentiated tumors using SEER Medicare data, no significant differences were noted between immediate treatment with primary ADT versus observation with regard to overall mortality (adjusted HR: 1.04; 95% CI 0.97 to 1.13) or prostate cancer-specific mortality (adjusted HR: 1.12; 95% CI: 0.96 to 1.29).157 Of note, in one trial, patients with clinically localized prostate cancer who were unfit for (or declined) local treatment were randomized to immediate versus delayed (at the time of symptomatic progression or metastatic disease) ADT.162 Although the trial did not report outcomes specifically for patients with high-risk prostate cancer, immediate treatment with ADT was associated with a decrease in overall mortality (HR: 0.80; 95% CI: 0.68 to 0.95), but not prostate cancer-specific mortality (10-year incidence 24.8% versus 26.0%, p=0.44) or disease progression. Further, the study was rated as having moderate risk of bias due to open-label design and unclear blinding of outcomes. For such patients, the primary goals of care include symptom control/palliation and maintenance of QOL. As such, ADT may be used to manage urinary tract sequelae of local tumor growth through (albeit transient) cytoreduction.