ECP 2023 Abstracts

S143 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 tools. Herein, we assess their impact in prostatectomies on bio- chemical recurrence (BCR) using CAPRA post-surgical (CAPRA- S) stratification. Methods: 826 prostatectomy cases diagnosed with PCa between 2010 and 2018 in two North American cohorts were retrospectively assessed for presence of CC/IDC. CAPRA-S scores were calculated and strati- fied into low (0-2), intermediate (3-5) and high (6-10) risk groups. BCR was compared between cases with and without CC/IDC using Cox model statistics. Prognostic performance was evaluated using Har- rell’s c-index. Results: 826 cases: Grade group (GG) 1, n=94; GG2, n=476; GG3, n=185; GG4, n=13; GG5, n=58. Median follow-up time, 4.2 years (range 2.9-6.4). There were 341 (41%) CC/IDC cases, and 166 (20%) BCR. The CAPRA-S low, intermediate, and high risk groups com- prised 356 (43%), 329 (40%), and 141 (17%) cases. CAPRA-S scores discriminated the three risk groups for BCR (p<0.001). Addition of CC/IDC significantly improved stratification of the CAPRA-S inter- mediate-risk group for BCR (HR 2.27, 95% CI 1.40-3.66) as well as overall c-index (0.689 vs 0.667, ANOVA p<0.001). CC/IDC had no significant impact amongst the low-risk group, and inconclusive effects in the high-risk group likely due to small data volume. Conclusion: The integration of CC/IDC into the CAPRA-S tool led to substantial improvement of post-surgical patient stratification for BCR in cases with CAPRA-S score 3-5 (intermediate-risk group). This sug- gests CC and IDC are relevant prognostic biomarkers to be included in future prostate cancer stratification tools. A larger, more diverse cohort with longer follow-up would allow us to better evaluate the impact of CC/IDC in predicting BCR in the CAPRA-S high-risk group and in predicting event-free survival across all risk groups. PS-26-024 MTAP status in a non-muscle invasive bladder cohort: correlation with grade, subtype and progression A. Oberc*, E. Olkhov-Mitsel, E. Slodkowska, K.J. Craddock, M.R.D. Downes *University of Toronto, Canada Background & objectives: Methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) is a surrogate for CDKN2A deletions which have been associated with adverse outcomes in bladder cancer. We assessed how MTAP IHC correlated with grade, molecular subtypes, and clinical outcomes in non-muscle invasive bladder cancer (NMIBC). Methods: 74 resection and biopsy specimens of NMIBC were graded using a three-tier hybrid system. MTAP IHC (Abnova, clone 2G4) was interpreted as negative when carcinoma completely lacked MTAP expression. Molecular subtype was defined as basal, luminal-URO and luminal-GU using CK5/6, GATA3, and p16 IHC. Progression free (PFS) and recurrence free survival (RFS) were assessed. Results: There were 56 luminal-URO, 18 luminal-GU, 0 basal and 25 low grade, 21 high grade 2, 28 high grade 3 cases. Luminal-GU was associated with decreased PFS (p=0.003) and RFS (p=0.047) com- pared to luminal-URO. High grade 2 and 3 had reduced PFS (p=0.006) but no significant change in RFS compared to low grade. Low grade was associated with luminal-URO, whereas high grade 3 was associ- ated with luminal-GU (p=0.030). MTAP loss was only identified in luminal-URO (22/56 cases vs 0/18 Luminal-GU). When MTAP sta- tus is combined with subtype, luminal-URO with MTAP loss shows an intermediate PFS between MTAP-intact URO and luminal-GU (p=0.007). Conclusion: High grade and luminal-GU subtype were associated with progression to muscle invasion or beyond (≥ pT2). We established MTAP loss occurs exclusively in the luminal-URO subtype, similar to findings in muscle invasive bladder cancer, and that MTAP loss reduces PFS. This suggests that MTAP may be a relevant prognostic biomarker in luminal-URO NMIBC and could help in determining frequency of follow up and management in the most common molecular subgroup of NMIBC. PS-26-025 Transrectal ultrasound prostate biopsy is associated with higher rates of Gleason grade group concordance in prostatic adenocarci- noma compared with transperineal biopsy: a retrospective cohort series from a tertiary referral centre P. Reddy*, N. Swan, T. Crotty, D. Galvin *Histopathology Department, St Vincent’s University Hospital, Ireland Background & objectives: Prostate biopsy (PB) Gleason grade group (GGG) scoring is a key parameter for diagnosis, risk stratification and management decisions in prostate cancer. Our study investigated whether PB method affects the concordance rates of GGG between PB and radical prostatectomy (RP). Methods: Our study included 588 patients who underwent RP from January 2018 to December 2022. We collected data from histology reports on biopsy method, age, GGG on PB, GGG on RP, surgical margin status and the presence of extra-prostatic extension (EPE). Sta- tistical analysis was performed using a chi-square test for categorical variables and Mann Whitney U test for continuous variables. Results: The median age at RP was 62 years. Transrectal ultrasound biopsy (TRUS) was performed in 72% of cases, while transperineal biopsy (TP) was used in 21%. Overall concordance was observed in 58% of cases, with 22% upgraded and 20% downgraded. GGG 4 was the least predictive group, with 68% of these cases assigned a different GGG at RP. GGG upgrading was more frequent in TP compared with TRUS biopsy (55% vs 33%) and this method of biopsy was significantly associated with GGG upgrading (p=0.01). EPE and seminal vesicle involvement (SVI) were also associated with GGG upgrading (p=0.01 and p=0.01). Surgical margin status was not significantly related to GGG upgrading (p=0.48). Conclusion: Our study further highlights that GGG discordance between PB and RP is a common occurrence. While our study is lim- ited in size, it demonstrates a significantly higher rate of upgrading in TP compared with TRUS. This finding emphasises the need for further investigation into the relationship between biopsy method and GGG upgrading. We also highlight other factors associated with GGG upgrading, namely the presence of EPE and SVI. These may assist management decisions at multidisciplinary team meetings. PS-26-026 Predictors of cancer-specific mortality in pT1 urothelial bladder cancer: 50 months follow-up in 284 cases A. Ristic Petrovic*, S. Stojnev, M. Potic Floranovic, I. Conic, M. Krstic, L. Jankovic Velickovic *University Clinical Centre Nis, Medical Faculty University of Nis, Serbia Background&objectives: Treatment of pT1 bladder cancer should be per- sonalized from the beginning in order to preserve functional bladder. Molec- ular pathways activated in hypoxia personalize response to radio/chemother- apy. NOTCH3 contributes chemotherapy resistance and NOTCH3-HIF1α interaction leads to hypoxia-induced resistance to radiotherapy. Methods: The immunohistochemical expression of HIF1 alpha, VEGFR1, and NOTCH3 was evaluated in 284 pT1 bladder cancer sam- ples, incorporated in tissue microarrays. HIF1-alpha was assessed through nuclear staining, VEGFR1 through cytoplasmic expression, while for NOTCH3 membranous expression was declared as positive. Micro-vessel density was estimated through counting the CD34 positive micro-vessels. Results: After a mean follow-up of 50 months, in 284 patients diag- nosed with pT1 bladder cancer, we found independent predictors of cancer specific mortality: older age, high grade, presence of diver- gent differentiation, especially squamous, concomitant carcinoma in situ, smoking, dysuria as the first symptom, all types off treatment