Apparent Diffusion Coefficient as an Early Predictive Factor of Local and Overall Response to Treatment with Androgen Deprivation Therapy and Radiotherapy in Patients with Prostate Cancer

Abstract

Background/Objectives: To analyze the predictive value of the apparent diffusion coefficient (ADC) in patients with prostate cancer (PCa) treated with radiotherapy (RT) and androgen deprivation therapy (ADT). Methods: Retrospective study of patients with high-risk, very high-risk, or unfavorable intermediate-risk PCa who received RT and ADT between 2008 and 2019 and underwent multiparametric magnetic resonance imaging mpMRI) at 6 months post-RT. Differences in ADC values were compared between patients with and without progression and/or local recurrence. Receiver operating characteristic (ROC) curves were used to obtain ADC cutoffs for predicting 10-year progression-free-survival (PFS) and local recurrence-free survival (LRFS). Results: We evaluated 98 patients (73 [74.5%] high-risk). Over a mean ± SD follow-up of 95.36 ± 30.54 months, 19 patients (19.4%) progressed; at 10 years, PFS was 75.6%, LRFS 93.8%, metastasis-free survival 85.5%, and overall survival 89.5%. Post-RT ADC was significantly lower in patients with local recurrence (1.09 ± 0.18 vs. 1.30 ± 0.20 × 10^-3 mm²/s, p = 0.020) and progression (1.23 ± 0.20 vs. 1.30 ± 0.21 × 10^-3 mm²/s, p = 0.004). ROC analysis identified a post-RT ADC cutoff of 1.11 × 10^-3 mm²/s for local recurrence (area under curve [AUC] 0.843, sensitivity 89.4%, positive predictive value [PPV] 98.8%). The cutoff for progression was 1.24 × 10^-3 mm²/s (AUC0.705, sensitivity 72.2%, PPV87.7%). Patients with a post-RT ADC value below and above 1.11 × 10^-3 mm²/shad a 10-year LRFS of 66.8% and 97.7%, respectively (HR: 25.04 [2.58-242.92], p < 0.001). The corresponding rates for 10-year PFS were 58.6% and 85.6% in patients with post-RT ADC values below and above 1.24 × 10^-3 mm²/s (HR: 2.916 [1.113-7.644], p = 0.015). In the multivariate analysis, a post-treatment ADC value ≤ 1.24 × 10^-3 mm²/s was a significant prognostic factor for a lower PFS (HR: 3823 [1371-10,657], p = 0.010). Conclusions: This is the first study to show that post-RT ADC can be a predictive factor of local recurrence in PCa treated with RT and ADT. Moreover, this long-term study demonstrates its value as a predictive factor of progression in PCa treated with RT and ADT.

Keywords: androgen deprivation therapy; apparent diffusion coefficient; multiparametric magnetic resonance imaging; prostate cancer; radiotherapy.

Figure 1

Differences in ADC values at diagnosis and post-RT between patients with intermediate- and high-risk prostate cancer (A,B) and patients with a Gleason score ≤ 7 and ≥8 (C,D).

Figure 1

Differences in ADC values at diagnosis and post-RT between patients with intermediate- and high-risk prostate cancer (A,B) and patients with a Gleason score ≤ 7 and ≥8 (C,D).

Figure 2

Relative changes in ADC values from diagnosis to post-RT. The figures show patients with local recurrence (orange) and any form of progression (blue).

Figure 3

(A) Receiver operating characteristic analysis for local recurrence-free survival. (B) Kaplan–Meier curves for progression-free survival in patients with an ADC value ≤ 1.11 vs. >1.11 × 10⁻³ mm²/s.

Figure 4

(A) Receiver operating characteristic analysis for progression-free survival. (B) Kaplan–Meier curves for progression-free survival in patients with an ADC value ≤ 1.24 vs. >1.24 × 10⁻³ mm²/s.