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Prostate cancer active surveillance: Better patient risk stratification and use of imaging

Presented By
Dr Todd Morgan, Dr Vasilis Stavrinides, Dr Marco Bandini
EAU 2019
Appears to be safe to expand indication for active surveillance (AS) to Gleason 3+4, but the data on using MRI instead of biopsy in AS are not yet clear.

The 6 Movember Global Action Plan (GAP) consortia are worldwide collaborations between researchers in prostate and testicular cancer tackling questions of unmet needs: biomarkers (GAP1), imaging (GAP2), active surveillance (AS, GAP3), exercise and metabolic health (GAP4), testicular cancer (GAP5), and oligometastatic prostate cancer (GAP6). At EAU19, the Movember GAP3 consortium (Dr Todd Morgan, University of Michigan at Ann Arbor, USA presenting for Hellman et al.) reported on 7,704 men being followed by AS from 14 centres: 6,725 men with Grade Group (GG)1 3+3 disease (87%) and 979 men with GG2 3+4 disease (13%). Discontinuation of AS (40% GG1 vs 50% GG2) was attributable to: switch to active treatment due to progression (19% vs 23%), switch to active treatment without evidence of progression (11% vs 18%), adverse pathology (34% GG1 vs 42% GG2). Future studies will better stratify intermediate risk disease by MRI and genomic profiling (e.g. BRCA2 or ATM gene mutations), which will further elucidate to what extent AS can be expanded to more men with Gleason 3+4 prostate cancer.

Dr Vasilis Stavrinides et al. (University College London, United Kingdom) reported on their AS cohort (n=626) which includes Gleason 3+3 or low-volume 3+4, provided PSA <20 ng/mL and baseline multiparametric MRI scan (mpMRI). The group could conclude that MRI-visible disease was associated with significantly shorter time to AS exit (median follow-up 53 months). A single PCa-related death was reported in their study period. Interestingly, in a subgroup analysis, if a patient was mpMRI-negative upfront, it made little to no difference if their disease was 3+3 or 3+4. These data again indicate expansion of AS to 3+4 prostate cancer.

Yet another study supported this same conclusion. Dr Marco Bandini and colleagues (Università Vita-Salute San Raffaele, Italy) prospectively enrolled 174 patients with D’Amico low-risk prostate cancer (PSA <10 ng/mL, cT ≤2, and biopsy Gleason Score 6). mpMRI of a visible lesion (HR=2.31, P=0.003) upfront was a significant indicator and was more important than any other biopsy pathology parameter.

Another hot topic actively discussed was: can we reduce the number of biopsies by applying mpMRI during follow-up? The data presented at the EAU were somewhat contradictory on this topic (see Table). The first studies in the Table indicate that a stable lesion being followed by active surveillance with MRI has a very small chance of being missed should it grow. However, the fact that you might miss up to 35% cases of prostate cancer if you do not do biopsy in the presence of a normal MRI (Osses et al.), is alarming. In short, there is a discrepancy regarding whether it is safe to rule out biopsy in the active surveillance setting, and we are not yet ready for a full paradigm-shift towards mpMRI for follow-up.

Table: Overview of contradictory results concerning the value of mpMRI vs biopsy at EAU 2019.

Green text indicates studies supporting mpMRI in follow-up; red text has mixed or negative data. AS, active surveillance; Bx, biopsy; GG, Grade Group; mpMRI, multiparametric; NPV, negative predictive values; PPV, positive predictive values; TBx, Targeted biopsy; TRUS, transrectal ultrasonography.

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