The dose distribution in dominant intraprostatic tumour lesions defined by multiparametric MRI and PSMA PET/CT correlates with the outcome in patients treated with primary radiation therapy for prostate cancer

BACKGROUND: We hypothesized that dominant intraprostatic lesions (DILs) could be depictured by multimodal imaging techniques (MRI and/or PSMA PET/CT) in patients with primary prostate cancer (PCa) and investigated possible effects of radiotherapy (RT) dose distribution within the DILs on the patients’ outcome. METHODS: One hundred thirty-eight patients with localized prostate cancer (PCa) and visible DIL underwent primary external beam RT between 2008 and 2016 with an aimed prescription dose of 76 Gy to the whole prostate. Seventy-five patients (54%) additionally received androgen deprivation therapy. Three volumes were retrospectively generated: DIL using pretreatment MRI and/or PSMA PET/CT, prostatic gland (PG) and the subtraction between PG and DIL (SPG). The minimum dose (Dmin), maximum dose (Dmax) and mean dose (Dmean) in the three respective volumes were calculated. Biochemical recurrence free survival (BRFS) was considered in uni- and multivariate Cox regression analyses. An explorative analysis was performed to determine cut-off values for the three dose parameters in the three respective volumes. RESULTS: With a median follow-up of 45 months (14–116 months) 15.9% of patients experienced BR. Dmin (cut-off: 70.6 Gy, HR = 0.39, p = 0.036) applied to the DIL had an impact on BRFS in multivariate analysis, in contrast to the Dmin delivered to PG and SPG which had no significant impact (p > 0.05). Dmin was significantly (p < 0.004) lower in patients with BR than in patients without BR. Dmax within DIL-imaging (cut-off: 75.8 Gy, HR = 0.31, p = 0.009) and in both PG und SPG (cut-off: 76 Gy, HR = 0.32, p = 0.009) had a significant impact on the BRFS. 95% of patients with a Dmax ≥76 Gy in SPG had a Dmin ≥70.6 Gy in DIL-imaging. Dmean in all of the three volumes had no significant impact on BRFS (p > 0.05). CONCLUSIONS: The dose distribution within DILs defined by PSMA PET/CT and/or MRI is an independent risk factor for BR after primary RT in patients with PCa. These findings support the implementation of imaging based DIL interpretation for RT treatment planning, although further validation in larger patient cohorts with longer follow-up is needed.