Prostate cancer is the most common nondermatologic cancer in men. In 2007 an estimated 218,890 men were diagnosed with, and 27,050 deaths were attributed to, prostate cancer in the United States. Approximately 90 percent of men with prostate cancer have disease considered confined to the prostate gland (clinically localized disease). Reported prostate cancer incidence has increased with introduction of the prostate-specific antigen (PSA) blood test. Disease specific mortality rates have declined, and an estimated 1.8 million men living in the United States have a diagnosis of prostate cancer. Clinically detected prostate cancer is primarily a disease of elderly men. Prostate cancer frequently has a relatively protracted course even if left untreated, and many men die with, rather than from, prostate cancer. Largely because of widespread PSA testing, the lifetime risk of being detected with prostate cancer in the United States has nearly doubled to 20 percent. However, the risk of dying of prostate cancer has remained at approximately 3 percent. Therefore, considerable overdetection and treatment may exist. The primary goal of treatment is to target the men most likely to need intervention in order to prevent prostate cancer death and disability while minimizing intervention-related complications. Common treatments include watchful waiting (active surveillance), surgery to remove the prostate gland (radical prostatectomy), external beam radiotherapy (EBRT) and interstitial radiotherapy (brachytherapy), freezing the prostate (cryotherapy), and androgen deprivation therapy (ADT). All treatments have risks of complications, although frequency and severity may vary. Patient treatment decisionmaking incorporates physician recommendations and estimated likelihood of cancer progression without treatment, as well as treatment-related convenience, costs, and potential for eradication and adverse effects (AEs). Patient characteristics, including race/ethnicity, age, and comorbidities, have an important role in predicting mortality; the likelihood of treatment-related urinary, bowel, and sexual dysfunction; treatment tradeoff preferences; and selection. However, little is known about how these characteristics modify the effect of treatment. Prior to the advent of widespread PSA testing, most prostate cancers were detected based on abnormalities on the digital rectal examination (DRE) or incidentally from tissue obtained at surgery for treatment of symptoms due to benign prostatic obstruction. The vast majority of prostate cancers currently detected in the United States are asymptomatic, clinically localized, and found on routine PSA testing. PSA testing detects more tumors, at an earlier stage, with smaller volume within each stage, and at an earlier period in a man's life than non-screen detected tumors. The clinical significance, natural history, and comparative effectiveness of treatments in PSA-detected cancers are not known but likely differ from those detected and treated in the pre-PSA era (before the late 1980s to early 1990s). This report summarizes evidence comparing the relative effectiveness and safety of treatment options for clinically localized prostate cancer. The report addresses the following questions: 1. What are the comparative risks, benefits, short- and long-term outcomes of therapies for clinically localized prostate cancer? 2. How do specific patient characteristics, e.g., age, race/ethnicity, presence or absence of comorbid illness, preferences (e.g., tradeoff of treatment-related adverse effects vs. potential for disease progression), affect the outcomes of these therapies, overall and differentially? 3. How do provider/hospital characteristics affect outcomes overall and differentially (e.g., geographic region and volume)? 4. How do tumor characteristics, e.g., Gleason score, tumor volume, screen vs. clinically detected tumors, affect the outcomes of these therapies, overall and differentially?