Life style and interaction with microbiota in prostate cancer patients undergoing radiotherapy: study protocol for a randomized controlled trial
Authors: Gnagnarella Patrizia , Marvaso Giulia , Jereczek-Fossa Barbara Alicja , de Cobelli Ottavio , Simoncini Maria Claudia , Nevola Teixeira Luiz Felipe , Sabbatini Annarita , Pravettoni Gabriella , Johansson Harriet , Nezi Luigi , Muto Paolo , Borzillo Valentina , Celentano Egidio , Crispo Anna , Pinto Monica , Cavalcanti Ernesta , Gandini Sara ,   for the MicroStyle Collaborative Group, Gavioli Costanza , Ciceri Silvia , Latella Marialetizia , Corrao Giulia , Zerini Dario , Macis Debora , Aristarco Valentina , Cozzi Gabriele , Mazzocco Ketti , Iuliana Fodor Cristiana , Galiè Serena , Catozzi Carlotta , Di Franco Rossella , De Martino Nunzio , Grimaldi Maria , Montagnese Concetta , Prete Melania , Nocerino Flavia , Rotondo Emanuela , Arpino Sergio , Meola Serena , Labonia Francesco , Bellerba Federica 
Published: July 2022

Abstract
Background
Prostate cancer (PCa) is the second most common cancer in men worldwide. The standard non-surgical approach for localized PCa is radiotherapy (RT), but one of the limitations of high-dose RT is the potential increase in gastrointestinal and genitourinary toxicities. We present the protocol of the Microstyle study, a multicentre randomized two-arm crossover clinical trial. The primary outcome will be assessed at the end of 6-month intervention, by measuring the change in adherence to a healthy lifestyle score. The hypothesis is that modifying lifestyle we change microbiome and improve quality of life and decrease side effects of RT.

Methods
Study participants will be recruited among men undergoing RT in two Italian centers (Milan and Naples). We foresee to randomize 300 patients in two intervention arms: Intervention Group (IG) and Control Group (CG). Participants allocated to the IG will meet a dietitian and a physiotherapist before RT to receive personalized diet and exercise recommendations, according to their health status, to improve overall lifestyle and reduce side effects (bowel and/or urinary problems). Dietitian and physiotherapist will work together to set individualized goals to reduce or eliminate side effects and pain according to their health status. All participants (IG) will be given a pedometer device (steps counter) in order to monitor and to spur participants to increase physical activity and reduce sedentary behavior. Participants included in the CG will receive baseline general advice and materials available for patients undergoing RT. According to the cross-over design, the CG will cross to the intervention approach after 6-month, to actively enhance compliance towards suggested lifestyle recommendations for all patients.

Discussion
This trial is innovative in its design because we propose a lifestyle intervention during RT, that includes both dietary and physical activity counselling, as well as monitoring changes in microbiome and serum biomarkers. The promotion of healthy behaviour will be initiated before initiation of standard care, to achieve long lasting effects, controlling side effects, coping with feelings of anxiety and depression and improve efficacy of RT.

Trial registration
ClincalTrial.gov registration number: NCT05155618. Retrospectively registered on December 13, 2021. The first patient was enrolled on October 22, 2021.