Histopathological Correlation with Multi-Parametric MRI: Clinical Implications for Focal Prostate Radiation Therapy Treatment Planning on a Prospective Trial

Abstract

While the feasibility of MRI-guided focal prostate therapy has recently been demonstrated, significant concern persists regarding the sensitivity of multi-parametric MRI (mpMRI) in revealing the full extent of disease. As a result, the appropriate population for partial gland therapy remains unknown. We conducted tandem prospective pilot trials investigating the correlation of initial sextant biopsies and mpMRI with targeted and comprehensive biopsies, and the resulting radiotherapeutic treatment implications. Patients with diagnostic biopsies revealing focal Gleason 6-7 disease and staging mpMRI (including T2, DWI and DCE sequences) showing a concordant PIRADS 4-5 lesion were eligible. Biopsies were performed using MRI/trans-rectal ultrasound fusion under electromagnetic sensor navigation, targeting the four corners and center of the MRI lesion, in addition to 12 whole-gland confirmatory biopsies. A cohort of six patients underwent confirmatory biopsies to assess reliability of their standard workup, and eight additional patients were considered for focal prostate SBRT on protocol if histopathology was concordant with initial biopsies and mpMRI. Significance of correlation was analyzed using Fisher’s exact test and Pearson’s chi square. Of the 14 patients enrolled, five had Gleason 6 and nine had Gleason 3+4 disease at diagnosis, with a mean PSA of 5.95 ± 1.72 (mean age: 64.3 years). Absolute concordance of histopathology on targeted and repeat whole gland biopsies was demonstrated in 28.6% of patients, 2/6 in the first group and 2/8 on the subsequent therapeutic protocol (Fisher's p = 0.006; Pearson's p = 0.012). One patient was disqualified due to a prohibitively elevated IPSS. Among the 9 broadly discordant cases (69.2%), three had an additional site of Gleason 6 disease, one had a second site of ipsilateral Gleason 3+4, one had contralateral Gleason 4+3, one had diffuse Gleason 7-9 disease and one had high volume Gleason 8 disease within the target lesion. In two cases, the targeted biopsy was negative for malignancy. Three patients (21.4%, Fisher's p = 0.085, Pearson's p = 0.170) were upstaged to a new NCCN risk category (low → intermediate; low → high; intermediate → high), necessitating substantial modifications in treatment recommendations, including androgen deprivation therapy and targeting of the seminal vesicles. Confirmatory targeted and whole-gland biopsies of initially pathologically and radiographically focal prostate adenocarcinoma revealed additional sites of disease in the majority of patients, and a subset were upstaged with clinical and therapeutic implications. These results suggest that focal therapy or dose escalation based on MRI sequencing may benefit from precise histopathologic correlation, which is currently being further investigated in a national cooperative group prospective clinical trial.