Background: Prostate cancer patients on hormonal therapy experience significant treatment-related physical and psychological sequelae. Purpose: We examined moderator variables to determine whether certain participants demonstrated quality of life (QOL) benefits from a group-based lifestyle physical activity program compared to a group-based educational support program and standard care. Methods: Participants were 134 prostate cancer patients on continuous androgen ablation in a controlled trial that used adaptive allocation. Results: As reported elsewhere, no significant differences were found between study conditions on primary QOL outcomes following the 6-month interventions. However, in a secondary analysis, several significant interactions indicated that both group programs benefited patients with lower psychosocial functioning at baseline; patients with lower mental health and social support scores had significant improvements in these measures compared with standard care. For those with higher pain, the educational support program resulted in significant improvements compared with the other two conditions. Twelve-month findings indicated lasting effects. Conclusions: Consistent with existing research, results indicate that group interventions benefit cancer patients with limitations in psychosocial functioning. Findings underscore the importance of physical activity/exercise studies to employ control conditions that consider the attention and support provided by health educators and group members, particularly when examining psychosocial outcomes and pain.