Strategic Endocrine Therapy and Targeted Radiotherapy for Prostate Cancer

Definitive radiation therapy combined with hormone therapy improves oncologic outcomes in patients with high-risk prostate cancer. However, hormone therapy has substantial toxicity, including metabolic and cardiovascular, and negatively impacts quality-of-life. Previous trials demonstrated that long-term hormone therapy lasting 18-36 months improved overall survival compared to short-term hormone therapy lasting only 4-6 months. However, long-term hormone therapy also extends the duration of treatment-related toxicity. There is great interest among patients and physicians to reduce the total treatment time. A trial studying shorter duration of hormone therapy is warranted for the following reasons. First, the trials that established the benefits of long-term hormone therapy were conducted over 20 years ago. Since then, advances in staging imaging and image-guided biopsy techniques have led to major stage migration in prostate cancer that has improved the prognosis of patients with disease categorized as high risk but localized. Second, substantial improvements in radiotherapy techniques have made it possible to deliver higher, more ablative radiation doses to the tumor while sparing normal organs. Third, even recurrent disease after definitive radiotherapy can now be detected early and managed with advanced radiotherapy (stereotactic ablative radiotherapy) to delay a need for salvage hormone therapy. Fourth, recent randomized trials have demonstrated that combining conventional androgen-deprivation therapy - usually accomplished with a gonadotropin-releasing hormone agonist or antagonist - with an androgen receptor pathway inhibitor is safe and improves overall survival in advanced prostate cancer. These advances suggest that modern radiotherapy combined with short-term androgen deprivation therapy - and an optional androgen receptor pathway inhibitor - may achieve outcomes comparable to radiotherapy with long-term androgen deprivation therapy. This strategy offers the potential to maintain tumor control, reduce treatment-related morbidity, and improve patient survivorship. This randomized trial will compare the efficacy and toxicity of this novel treatment approach against the current standard of care. The investigators hypothesize that the novel treatment approach will have excellent disease control - comparable to that achieved with traditional long term androgen deprivation therapy - while improving quality of life.