The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.
Cancers. 2022 May 31*** epublish ***
Dimple Chakravarty, Parita Ratnani, Li Huang, Zachary Dovey, Stanislaw Sobotka, Roy Berryhill, Harri Merisaari, Majd Al Shaarani, Richa Rai, Ivan Jambor, Kamlesh K Yadav, Sandeep Mittan, Sneha Parekh, Julia Kodysh, Vinayak Wagaskar, Rachel Brody, Carlos Cordon-Cardo, Dmitry Rykunov, Boris Reva, Elai Davicioni, Peter Wiklund, Nina Bhardwaj, Sujit S Nair, Ashutosh K Tewari
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510275, China., Department of Radiology, University of Turku, 20014 Turku, Finland., Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Department of Hematology & Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Division of Cardiovascular Research, Albert Einstein College of Medicine, New York, NY 10467, USA., Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Decipher Biosciences, A Subsidiary of Veracyte Inc., South San Francisco, CA 94080, USA.