404 Neoplasma 2022; 69(2): 404–411 doi:10.4149/neo_2021_210622N828 Correlation between radiological and biological features and clinical outcomes in early prostate cancer: an exploratory subgroup analysis Giulia CORRAO 1,2,# , Giulia MARVASO 1,2,# , Mattia ZAFFARONI 1, *, Stefania VOLPE 1,2 , Matteo AUGUGLIARO 1 , Cristiana Iuliana FODOR 1 , Dario ZERINI 1 , Andrea VINGIANI 2,3 , Francesco Alessandro MISTRETTA 4 , Stefano LUZZAGO 4 , Sarah ALESSI 5 , Paola PRICOLO 5 , Gennaro MUSI 2,4 , Ottavio DE COBELLI 2,4 , Giuseppe RENNE 3 , Marco MANZONI 3 , Giuseppe PETRALIA 2,6 , Roberto ORECCHIA 7 , Barbara Alicja JERECZEK-FOSSA 1,2 1 Department of Radiation Oncology, European Institute of Oncology IRCCS, Milan, Italy; 2 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; 3 Department of Pathology, European Institute of Oncology IRCCS, Milan, Italy; 4 Division of Urology, Eu- ropean Institute of Oncology IRCCS, Milan, Italy; 5 Department of Radiology, European Institute of Oncology IRCCS, Milan, Italy; 6 Precision Imaging and Research Unit, Department of Medical Imaging and Radiation Sciences, European Institute of Oncology IRCCS, Milan, Italy; 7 Scientific Direction, European Institute of Oncology IRCCS, Milan, Italy *Correspondence: mattia.zaffaroni@ieo.it # Contributed equally to this work. Received June 22, 2021 / Accepted August 23, 20219 PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (PCa). In the same manner, multiparametric magnetic resonance imaging (mp-MRI) guided core biopsy is a powerful tool for PCa detection and staging. e aim of the study is to assess whether a correlation can be identified between the pathological stage defined by an mp-MRI-guided core biopsy and Ki-67 expression and PTEN deletion. Such correlation might be useful for staging and treatment personalization in PCa. is investigation was conducted in the context of phase II clinical study “Short-term radiotherapy for early prostate cancer with a concomitant boost to the dominant lesion” (AIRC IG-13218), ClinicalTrials. gov identifier: NCT01913717. Nineteen patients underwent a further in-bore MRI-targeted core biopsy (MRI-TBx) on the dominant intraprostatic lesion (DIL); on this basis, an additional Gleason Score (GS) was determined. PTEN loss and Ki-67 expression on these samples were analyzed and correlated with both risk categories modifications and oncological outcomes (overall survival, biochemical and clinical relapse). GS was upgraded in 5 cases, with 4 patients re-classified as intermediate- risk and 1 patient as high-risk. e latter experienced a clinical local relapse. No correlations between up/down-staging, PTEN deletion, and Ki-67 expression were observed in this cohort. Further investigations are needed towards the identifica- tion of a pattern in the tumor aggressiveness-response in PCa treated with ultra-hypofractionated radiotherapy. Moreover, a possible relationship between biomarker analysis and imaging textural features could be explored. Key words: PTEN, Ki-67, biomarkers, early prostate cancer, mp-MRI Prostate cancer (PCa) is the most frequently diagnosed cancer in North American and European men [1]. Despite the use of advanced and combined approaches, a substantial percentage of patients do not respond to treatments [2]. e challenge for the future is to identify sub-classes of patients for which standard treatments could fail, in order to improve personalized strategies. Blood tests, histopathology markers, and imaging studies are contributing to realizing this transi- tion [3], and possibly will be gradually incorporated into clinical practice. Nowadays, multiparametric magnetic resonance imaging (mp-MRI) is the most accurate imaging technique for organ- confined PCa, with 80% sensitivity for tumor detection [4] (86% with tumors greater than 0.5 cm 3 ) [5]. Several MRI parameters can be considered for the radiological character- ization of the disease, namely: Prostate Imaging Reporting and Data System (PI-RADS), Extra-Prostatic Extension score (EPE), Apparent Diffusion Coefficient (ADC), number and position of Dominant Intraprostatic Lesion (DIL), prostate volume. e use of mp-MRI can be extended to MRI-guided target core biopsy on the highest PI-RADS DIL to deter- mine the correct staging through the higher Gleason Score (GS). is technique allows determining DIL histopatho- logical characteristics with high precision, in contrast with the more commonly used transrectal ultrasound core biopsy (TRUS). Currently, the assessment of risk classes, according to National Comprehensive Cancer Network (NCCN) guide- lines [6], is based on Prostate Specific Antigen (PSA) value,