The recent post published on our website has prompted a comment from the Heidelberg group referring to their 2019 article (1) which highlights the difficulty of evaluating the target volume before focal treatment of PCa.
The article reports the results of multiparametric MRI in 316 patients prior to prostate biopsy. Biopsies were targeted in MRI-detected abnormalities and also in the rest of the prostate using a protocol developed for trans-perineal biopsies with a median of 29 cores. In patients with a positive MRI, the authors report the detection of Gleason 4 grade outside the MRI visible lesion in 60% of cases. If a 10mm safety margin is applied around the MRI lesion, this rate drops to 18%. The authors deduce that it is high enough to maintain systematic and targeted biopsies in all patients, especially to select patients eligible for focal therapy.
Of note, the drastic reduction in the number of off-target positive biopsies when a 10mm margin is applied around the lesion is also reported in the recent article from the same group (2), but with a 99% cancer detection rate by performing 9 biopsies in and around the target, significantly higher than the 82% rate in the 2019 cohort (1). This difference means that Gleason 4 grade is detected in the first cohort more than 1 cm outside the MRI visible lesion in nearly 20% of cases and that this is not the case in the second cohort. A registration error during biopsy, always possible with a rigid or elastic fusion software, as we had experimented in one of our studies with an elastic fusion software (3), may explain this discrepancy. An underestimation of the size of the lesion on MRI (4) is another explanation, but a positive more than one centimeter outside the index lesion should lead to the suspicion that the tumor missed by MRI is a secondary tumor, distinct from the one visible on MRI (figure).
Figure : 57 years old man. PSA: 7 ng/ml. A-D: T2-weighted, Diffusion-weighted images and whole mount radical prostatectomy specimen. The index lesion (*) originates in the peripheral zone (PZ). The vicinity (arrowheads) is involved by tumor, but not visible on MRI. Eleven mm outside the index lesion, a secondary lesion is visible (white arrows). The left PZ area with restricted diffusion is benign. Gleason score was 3+4 with 20% Gleason grade 4 in all tumor foci. Note that the 10mm margin around the index lesion is justified to delineate the target volume for treatment. Most tumors located more than 10mm out of the index lesion are secondary lesions.
This hypothesis raises the issue of MRI undetected PCa with Gleason score 3+4. The significance of these tumors, whose percentage of grade 4 did not exceed 20% in our study (3), could be questioned (5). Given a more favorable genetic profile (6), these tumors might be assimilated to low-risk tumors and not seeing them on MRI may not have consequences on their management, especially if they are secondary tumors in a patient eligible for focal treatment of an index visible lesion.
This hypothesis will certainly need to be validated in other studies. In the meantime, to reconcile the data from the two Heidelberg group studies, one could suggest that a positive diagnosis of significant cancer is one thing and a patient's eligibility for focal treatment is another. A positive diagnosis can probably be made with targeted biopsies only, but eligibility for focal treatment without systematic biopsies is not yet validated.
1. Bonekamp D, Schelb P, Wiesenfarth M, Kuder TA, Deister F, Stenzinger A, et al. Histopathological to multiparametric MRI spatial mapping of extended systematic sextant and MR/TRUS-fusion-targeted biopsy of the prostate. Eur Radiol. 2019;29(4):1820-30.
2. Tschirdewahn S, Wiesenfarth M, Bonekamp D, Pullen L, Reis H, Panic A, et al. Detection of Significant Prostate Cancer Using Target Saturation in Transperineal Magnetic Resonance Imaging/Transrectal Ultrasonography-fusion Biopsy. Eur Urol Focus. 2020.
3. Delongchamps NB, Lefevre A, Bouazza N, Beuvon F, Legman P, Cornud F. Detection of significant prostate cancer with magnetic resonance targeted biopsies--should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care? J Urol. 2015;193(4):1198-204.
4. van Houdt PJ, Ghobadi G, Schoots IG, Heijmink S, de Jong J, van der Poel HG, et al. Histopathological Features of MRI-Invisible Regions of Prostate Cancer Lesions. J Magn Reson Imaging. 2020;51(4):1235-46.
5. De Visschere PJ, Naesens L, Libbrecht L, Van Praet C, Lumen N, Fonteyne V, et al. What kind of prostate cancers do we miss on multiparametric magnetic resonance imaging? Eur Radiol. 2016;26(4):1098-107.
6. Purysko AS, Magi-Galluzzi C, Mian OY, Sittenfeld S, Davicioni E, du Plessis M, et al. Correlation between MRI phenotypes and a genomic classifier of prostate cancer: preliminary findings. Eur Radiol. 2019;29(9):4861-70.