Integrating Apparent Diffusion Coefficient and Prostate-Specific Antigen as Prognostic Factors of Treatment Response to Androgen Deprivation Therapy and Radiotherapy in Prostate Cancer

<b>Purpose:</b> This study evaluates the combined prognostic value of the apparent diffusion coefficient (ADC) from multiparametric MRI (mpMRI) and prostate-specific antigen (PSA) levels at 6 months post-radiotherapy (RT) in assessing treatment response in prostate cancer patients treated with RT and androgen deprivation therapy (ADT). <b>Materials and Methods:</b> All prostate cancer patients classified as unfavorable intermediate-risk, high-risk, or very high-risk, according to NCCN criteria, who received ADT and RT between 2008 and 2019 and underwent mpMRI and PSA testing 6 months after RT were included. Patients were stratified into three profiles based on threshold PSA (≤ vs. >0.1 ng/mL) levels and ADC (≤ vs. >1.24 × 10^-3 mm²/s) values: Profile A: low PSA and high ADC; Profile B: either high PSA/high ADC or low ADC/low PSA; Profile C: high PSA and low ADC. Ten-year progression-free survival (PFS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier curves and multivariate Cox regression. <b>Results:</b> Ninety-eight consecutive patients were retrospectively analyzed, of which 73 (74.5%) were high-risk. After a mean follow-up of 95.3 months, 19 (19.39%) patients progressed. Ten-year PFS, MFS, and overall survival were 75.6%, 87%, and 89.5% respectively. Progression events were 9.1% (Profile A), 29.4% (Profile B), and 44.4% (Profile C). Eight-year PFS was 89.2% (profile A), 70.9% (profile B) HR: 3.021 (CI 95%: 1.031-8.849; <i>p</i> = 0.044) and 44.4% (profile C) HR: 6.145 (CI 95%: 1.645-22.955; <i>p</i> = 0.007). Multivariate analysis confirmed a higher risk of progression in patients from profile B with HR: 3.958 (CI 95%: 1.18-13.191; <i>p</i> = 0.025) and profile C with HR: 41.945 (CI 95%: 5.000-351.761; <i>p</i> < 0.001) compared to patients from profile A. Metastasis events were 5.5% (Profile A), 8.8% (Profile B), and 33.3% (Profile C). Eight-year MFS was 100% (profile A), 89.6% (profile B) HR: 1.373 (CI 95%: 0.277-6.811; <i>p</i> = 0.689), and 74.1% (profile C) HR: 5.566 (CI 95%: 1.119-27.692; <i>p</i> = 0.047). <b>Conclusions:</b> The integration of PSA response and ADC measures at 6 months post-RT provides an effective combined prognostic factor to identify patients at higher risk of relapse, supporting closer monitoring and potential treatment intensification.