TPS414 Background: While radical prostatectomy results in excellent survival in patients with low- and favorable intermediate-risk localized prostate cancer, the role of surgery in the setting of higher-risk disease remains controversial. Many unfavorable intermediate-, high- and very high-risk patients are treated with androgen deprivation therapy (ADT) in combination with radiation. Although surgery can be curative for these patients a subset will experience recurrence and has an increased risk of prostate cancer mortality. These recurrences result from either residual local disease and/or micrometastatic disease nondiagnosed. Neoadjuvant therapy may improve local disease control by downstaging the primary tumor, treat occult distant metastasis, facilitate surgical resection, reduce or delay need for post-surgery treatment and provide an in vivo assessment of response to treatment. Methods: COACTION is a prospective, randomized, open-label with blinded endpoint adjudication multicenter clinical trial to assess whether a neoadjuvant combined treatment with leuprorelin and darolutamide is superior to monotherapy in terms of complete or almost complete pathological response. Key inclusion criteria: age ≥ 18 years; unfavorable intermediate- or high-/very high-risk non metastatic prostate adenocarcinoma intended for surgery; ECOG PS ≤ 1; testosterone > 230 ng/dL; no prior prostate cancer treatment. 144 patients will be randomized 1:1:1 to three arms: darolutamide 600 mg PO BID for 24 weeks + leuprorelin 22.5 mg SC in 0 and 12 weeks; darolutamide 600 mg PO BID alone for 24 weeks; or leuprorelin 22.5 mg SC 0 and 12 weeks alone. Primary endpoint is the proportion of patients with minimal residual disease, defined as residual cancer burden (RCB) ≤ 0.25 cm 3 or complete pathological response. The study main analysis will compare the combination therapy group versus the pooled monotherapy groups. If null hypothesis is rejected, then the combination therapy group will be compared with either monotherapy group individually. Groups will be compared for the primary endpoint by a model from the binomial family and log link function will be used to generate risk ratios (RR) and 95% confidence intervals (CI). Models will be adjusted for the stratification variable (intermediate- versus high-risk groups), for age and race (white versus non-white). We anticipate that the proportion of patients with minimal residual disease will be 10% in the pooled monotherapy groups and 30% in the combination therapy groups. For an alpha error of 5% and 80% power, the study will need a total of 132 patients included in the analytical population (44 in each group). In order to compensate for losses and patients who do not undergo surgery, we decided to enroll a total of 144 patients. If all enrolled patients are included in the main analysis, the study will have 84% power to detect such difference. Clinical trial information: NCT06627530 .
Moura et al. (Sun,) studied this question.