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328 Background: Although one of the most important risk factors for prostate cancer (PCa) is a family history of the disease, there is a poor awareness of genetic risk. The aim of the current study is to investigate the awareness of genetic risk for PCa in men belonging to female families with germline variants in DNA-repair genes (DRGs). Methods: Data were extracted by a prospective observational study designed to select men with germline pathogenic variants (PVs) and offer them a dedicated PCa screening. The selection of probands was performed by genetic counseling and testing of male grade I relatives of female patients with a PVs. Male candidates were identified after reviewing the genealogical trees of all women who had received the diagnosis of breast and/or ovarian cancer and tested positive for a PVs. All the probands, 35-69 yrs old, who resulted positive for PVs were offered to participate to a specific PCa screening based on annually digital rectal examination (DRE), detection of PHI, which is a blood test including total PSA, free PSA, free/total PSA and -2proPSA, and multiparametric MRI. The primary outcome was the “willing to be tested”, defined as a proxy for male awareness of PCa risk. The secondary endpoint was the acceptance rate to be screened. Results: We reviewed the genealogical trees of breast/ovarian cancer female patients from January 2017 to December 2021 and we identified, over 1256 families, 139 positive cases for PVs in DRGs. Among 139 families, we identified 378 “healthy” 35-69 yrs old men, who were offered a genetic counseling, and if they agree a genetic testing. Overall 117/378 (31%) healthy males declared to be interested to be tested. Out of the 51 new tests (66 men already tested out of the study), we found 30 (58.8%) positive men. All the new positive tested men accepted to attend the PCa screening. Living in Northern Italy, having at least one child and higher (degree) level of education were the strongest predictors of willing for testing (p

TPS578 Background: Approximately 75-85% of vesical urothelial carcinomas are non-muscle invasive bladder cancers (NMIBC). The primary treatment is transurethral resection (TUR) followed by adjuvant intravesical therapies with immunotherapy (BCG) and/or chemotherapy agents (i.e. mitomycin C - MMC). Unfortunately, the response to intravesical treatments is variable and incomplete and there is a un-met clinical need to improve its efficacy for reducing the recurrence rate and progression to muscle invasive BC (MIBC). Recently, has been showed that MMC induces immunogenic cell death (ICD), determining the expression of specific damage signals, like HMGB1 molecule, that favors the phagocytosis of dying tumor cells, the activation of innate immune cells and the presentation of tumor antigens to T lymphocytes [1]. The identification of ICD as a novel immune-related mechanism of action of MMC could provide opportunities to optimize bladder cancer management by proposing the use of MMC in a “neoadjuvant” setting. The aim of current clinical trial is to test the hypothesis that the neoadjuvant instillation of MMC in patients with NMIBC may reduce the recurrence rate and/or progression to MIBC. Methods: This is a prospective phase III randomized clinical trial in patients with primary treatment-naïve NMIBC recruiting since March 2022 (EudraCT 2021-003751-42_studio ICH-013-MMC). Patients are randomized 1:1 to neo-adjuvant MMC or standard of care. Patients enrolled in the neo-MMC group receive two intravesical instillations of MMC (40 mg/40 ml saline) in the 2 weeks before (days: -14 and -7) the scheduled TUR (day: 0). After TUR, as for clinical practice, both controls and neoMMC subjects, undergo adjuvant treatment, if required, based on the histological evaluation of the tumor and following EAU/PMID: 33040478 guidelines. The primary endpoint of the study is to evaluate the efficacy of MMC neoadjuvant treatment in reducing the recurrence rate of BC calculated as the proportion of patients who achieve a complete response (no evidence of BC after 3, 6, 12 and 24 mo.). The secondary clinical endpoint will be the analysis of the rate of grade and stage progression to MIBC in case of recurrence and the correlation with specific biomarker (i.e. expression of HMGB1). Consider that the primary aim of the study is to see a reduction of relapse, leading to an HR of 0.6, estimating on the control group a 30% relapse free at 12 months. With equal-sized group, a two-sided significance level test (α =0.05) with power 80% power (β=0.2), and assume that recruitment was to be terminated after 12 months, with a 2-year follow up, the required sample size is approximate 160 patient, 80 in each group (control / neoMMC). References: 1. Oresta B, et al Sci Transl Med. Jan 6;13(575):eaba6110 Clinical trial information: EudraCT 2021-003751-42_studio ICH-013 (MMC) .

284 Background: The TMPRSS2:ERG gene fusion (T:E) is found in up to 70% of prostate cancers (PCa) and results in androgen dependent overexpression of ERG, promoting tumor growth. The early identification of T:E may be helpful even in low-risk PCa. Although T:E can be non-invasively detected in urine, its correlation with new imaging tools (MRI and high-frequency ultrasound) and clinical outcome remains vague.This study investigates T:E expression in patients scheduled for random/software-assisted MRI or micro-ultrasound (29Mhz) fusion biopsy. Methods: This is a prospective cohort study in patients with suspected PCa enrolled between 2016 and 2019, approved by local authorities with Prot. N. 336/19, 14/05/2019. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they had ³1 suspicious lesion (PI-RADS V.2 >2) at mpMRI or PRIMUS >2 at MICRO-US. For each patient, 1 prostatic core from the highest PI-RADS or PRIMUS lesion was collected for T:E analysis (a core from the right lobe in negative patients). Histological analyses were performed by experienced genitourinary pathologists. RNA was extracted from a dedicated fresh biopsy and RT-PCR was performed with different primer couples to detect the most frequent T:E fusions. All amplified products were checked by sequencing. Results: The cohort consists of 92 patients (median PSA 7.13 ng/ml, IQR 5.25-11.04 - average age 65ys), 81 with a diagnosis of PCa after biopsy. mpMRI was performed on 63 (68.5%) patients and was positive in 58 (92%), who underwent fusion biopsy. T:E fusion transcripts were detected in 23.5% of individuals with a diagnosis of PCa. Among patients positive for T:E, those analyzed by MRI were 100% positive (73% PI-RADS ≥4), those analyzed by MICRO-US were 83% positive. Sensitivity of the T:E assay for any PCa was 23.5%, specificity 100%, with negative and positive predicting values of 15% and 100%. There was no correlation between T:E and family history, PSA, PIRADS, PRI-MUS and Gleason score. Conclusions: Our finding showed a 100% of specificity making T:E an attractive tool for early cancer detection. In the future, identification of T:E in semen could represent a screening test for clinical stratification of patients with suspected PCa.

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( > 4ng/ml and > 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.

e16136Background: Stereotactic body radiotherapy (SBRT) is an interesting therapeutic approach for several sites of metastatic disease but few published data exist on local control rates in the con...

310 Background: The quality of transurethral resection of bladder tumors strongly determines patient’s tumor after-care and prognosis. En bloc resection of bladder tumors (ERBT) might improve staging quality, perioperative morbidity and influence tumor recurrence. This is the first European multi-center study which was initiated by ESUT and was conducted to evaluate the safety, efficacy and recurrence rates of electrical vs. laser ERBT. Methods: Transurethral ERBT was performed on 221 prospectively collected patients in six academic centers with either monopolar/bipolar current or holmium/thulium laser energy. Staging quality measured by detrusor muscle involvement, various perioperative/surgical parameters and 12 months follow-up data were analyzed. Results: 156 and 65 patients were treated with electrical and laser ERBT, respectively. Median tumor size was 2.1 cm with biggest up to 5 cm. Detrusor muscle was available in 97.3%. A switch to conventional TURBT was significantly more frequent in the electrical ERBT group (26.3% vs. 1.5%, p1 cm. Recurrence rates did not differ within both groups although the majority of recurrences were noticed out of the ERBT resection field. Laser device might be an alternative for the treatment of patients with higher risk of postoperative bleeding due to its efficient hemostatic effect.