{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:08:36Z","timestamp":1789132116481,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cDun\u0103rea de Jos\u201d University of Gala\u021bi"},{"id":[{"id":"https:\/\/ror.org\/052sta926","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Despite advances in prostate cancer (PC) radiotherapy, including intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT), genitourinary (GU) and gastrointestinal (GI) toxicities remain important complications. Identifying reliable predictors is essential for personalized treatment. Objective: The aim of this study was to summarize current evidence on clinical, dosimetric, immunological, and genetic predictors of acute and late GU and GI toxicities after PC radiotherapy. Materials and Methods: A structured literature review of studies published between 2000 and 2026 was conducted using PubMed, Scopus, and Europe PMC. Eligible studies included clinical investigations, randomized controlled trials, meta-analyses, and reviews assessing toxicity according to RTOG and\/or CTCAE criteria. Results: GU toxicity was associated with pretreatment International Prostate Symptom Score (IPSS), large prostate volume, prior TURP, smoking, alpha-blocker use, and bladder\/urethral dose. GI toxicity correlated with rectal dose\u2013volume parameters, anorectal irradiation, anticoagulant therapy, and cardiovascular comorbidities. Acute grade \u2265 2 toxicity predicts late toxicity. Preliminary data from small single-center cohorts associate elevated IL-6, TGF-\u03b21, TNF-\u03b1, and systemic immune-inflammation index with higher toxicity risk, and higher lymphocyte counts with lower risk; these findings require prospective validation. The PROSTOX radiogenomic signature is promising for the prediction of late GU toxicity but still requires independent external validation in larger, ethnically diverse cohorts with longer follow-up, and is not currently suitable for routine clinical decision-making. Conclusions: GU and GI toxicities have distinct predictive profiles. Integrating clinical, dosimetric, immunological, and genetic factors may improve personalized radiotherapy, although prospective multicenter validation remains necessary.<\/jats:p>","DOI":"10.3390\/life16091477","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:21Z","timestamp":1788452481000},"page":"1477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictive Factors for Acute and Late Genitourinary and Gastrointestinal Toxicity Following Modern Radiotherapy for Prostate Cancer: A Narrative Review of Clinical, Dosimetric, Immunological, and Genetic Determinants"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5881-5594","authenticated-orcid":false,"given":"Rares-Nicolae","family":"Vadana","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian-Cornel","family":"Maier","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7424-7986","authenticated-orcid":false,"given":"Lauren\u021biu","family":"Dr\u0103gu\u0219","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0218tefan","family":"Ro\u0219ca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona-Dana","family":"Mitincu-Caramfil","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Andreea","family":"Rahnea-Nita","sequence":"additional","affiliation":[{"name":"M Hospital, Str. Witting 10, 010903 Bucure\u0219ti, Romania"},{"name":"The Clinical Department, The Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Radiotherapy Department, \u201cSf. Apostol Andrei\u201d County Emergency Clinical Hospital, 800578 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Barzu","sequence":"additional","affiliation":[{"name":"Live Wins Association, 030923 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Mihalcia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8187-7984","authenticated-orcid":false,"given":"Laura-Florentina","family":"Rebegea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"},{"name":"The Clinical Department, The Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Radiotherapy Department, \u201cSf. Apostol Andrei\u201d County Emergency Clinical Hospital, 800578 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 Cancer Estimates: Data Sources, Methods, and a Snapshot of the Cancer Burden Worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1038\/s41598-025-88392-8","article-title":"Global Burden and Risk Factors of Male Cancers from 1990 to 2021, with Forecasts to 2040","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1200\/JCO.2025.43.5_suppl.325","article-title":"Global Spatiotemporal Trends in Prostate Cancer Burden and Its Socioeconomic Disparities: An Observational Study from 1990 to 2021","volume":"43","author":"Zhou","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Franco, J.V., Hwang, E.C., Jung, J.H., Vaimberg, O., Ilic, D., Cleves, A., and Dahm, P. (2026). Prostate-Specific Antigen (PSA) Test for Prostate Cancer Screening. Cochrane Database Syst. Rev., 5.","DOI":"10.1002\/14651858.CD004720.pub4"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.eururo.2024.11.013","article-title":"Recent Patterns and Trends in Global Prostate Cancer Incidence and Mortality: An Update","volume":"87","author":"Schafer","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/pros.70166","article-title":"Global Trends in Prostate Cancer Incidence Among Men Aged 55+ (1992\u20132021): An Age-Period-Cohort Analysis","volume":"86","author":"Han","year":"2026","journal-title":"Prostate"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2023.04.021","article-title":"2022 Update on Prostate Cancer Epidemiology and Risk Factors: A Systematic Review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0140-6736(25)02221-4","article-title":"Prostate Cancer","volume":"407","author":"Fonteyne","year":"2026","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rahnea-Nita, G., Dumitru, M., Nechifor, A., Rahnea-Nita, R.-A., Maier, A.-C., Andronache, L.F., Cernea, A., Rebegea, A., and Rebegea, L.-F. (2025). Synchronous\/Metachronous Prostate Cancer with Other Cancer Sites: The Experience of a Single Center in Romania. Medicina, 61.","DOI":"10.3390\/medicina61091666"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rahnea-Nita, R.A., Rebegea, L.F., Nechifor, A., Mare\u0219, C., Toma, R.-V., Stoian, A.-R., Ciuhu, A.-N., Andronache, L.-F., Constantin, G.B., and Rahnea-Nita, G. (2023). The Complexity of Treatments and the Multidisciplinary Team: A Rare Case of Long-Term Progression-Free Survival in Prostate Cancer Until Development of Liver and Brain Metastases. J. Clin. Med., 12.","DOI":"10.3390\/jcm12175579"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1200\/JCO.18.01097","article-title":"Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline","volume":"36","author":"Morgan","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S1470-2045(16)30102-4","article-title":"Conventional Versus Hypofractionated High-Dose Intensity-Modulated Radiotherapy for Prostate Cancer: 5-Year Outcomes of the Randomised, Non-Inferiority, Phase 3 CHHiP Trial","volume":"17","author":"Dearnaley","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2025.0228","article-title":"Prostate Cancer: A Review","volume":"333","author":"Raychaudhuri","year":"2025","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.eururo.2018.12.003","article-title":"Pelvic Complications After Prostate Cancer Radiation Therapy and Their Management: An International Collaborative Narrative Review","volume":"75","author":"Matta","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Paslaru, A.M., Bounegru, I., Plesea-Condratovici, C., Marius, M., and Ciubara, A. (2025). Proportion and Correlates of Psychiatric Morbidity Among Psychiatry-Assessed Oncology Inpatients. Diseases, 13.","DOI":"10.3390\/diseases13110350"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S1470-2045(24)00720-4","article-title":"The Interplay Between Acute and Late Toxicity Among Patients Receiving Prostate Radiotherapy: An Individual Patient Data Meta-Analysis of Six Randomised Trials","volume":"26","author":"Nikitas","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/jnci\/djz075","article-title":"Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy","volume":"112","author":"Kerns","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(11)70302-3","article-title":"Independent Validation of Genes and Polymorphisms Reported to Be Associated with Radiation Toxicity: A Prospective Analysis Study","volume":"13","author":"Barnett","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/095530099140113","article-title":"Changes in Peripheral Blood Lymphocyte Subsets in Patients Undergoing Radiotherapy","volume":"75","author":"Louagie","year":"1999","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0360-3016(99)00275-8","article-title":"Association of Prostate Size With Urinary Morbidity Following Mixed Conformal Neutron and Photon Irradiation","volume":"45","author":"Forman","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S1470-2045(25)00205-0","article-title":"Intensity-Modulated Moderately Hypofractionated Radiotherapy Versus Stereotactic Body Radiotherapy for Prostate Cancer (PACE-C): Early Toxicity Results from a Randomised, Open-Label, Phase 3, Non-Inferiority Trial","volume":"26","author":"Tree","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2403365","article-title":"Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer","volume":"391","author":"Griffin","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1158\/1078-0432.CCR-24-3951","article-title":"Validation and Derivation of miRNA-Based Germline Signatures Predicting Radiation Toxicity in Prostate Cancer","volume":"31","author":"Kishan","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Michalski, J.M., Moughan, J., Purdy, J., Bosch, W., Bruner, D.W., Bahary, J.-P., Lau, H., Duclos, M., Parliament, M., and Morton, G. (2018). Effect of Standard vs Dose-Escalated Radiation Therapy for Patients with Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol., 4.","DOI":"10.1001\/jamaoncol.2018.0039"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.ijrobp.2013.07.041","article-title":"Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial","volume":"87","author":"Michalski","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S1470-2045(15)00567-7","article-title":"Hypofractionated Versus Conventionally Fractionated Radiotherapy for Patients with Prostate Cancer (HYPRO): Late Toxicity Results from a Randomised, Non-Inferiority, Phase 3 Trial","volume":"17","author":"Aluwini","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhong, S., Liu, Y., Fang, H., Tang, P., Dai, J., Shou, J., and Li, Y. (2023). Ten-Year Outcomes of Hypofractionated (45 Gy in 9 Fractions) Intensity-Modulated Radiotherapy for Localized Prostate Cancer. J. Clin. Oncol., 41.","DOI":"10.1200\/JCO.2023.41.16_suppl.e17100"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S1470-2045(25)00656-4","article-title":"Ultra-Hypofractionated Versus Conventionally Fractionated Radiotherapy for Localised Prostate Cancer (HYPO-RT-PC): 10-Year Outcomes of an Open-Label, Randomised, Phase 3, Non-Inferiority Trial","volume":"27","author":"Nilsson","year":"2026","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ratnakumaran, R., Hinder, V., Brand, D., Staffurth, J., Hall, E., van As, N., and Tree, A. (2023). The Association Between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE-B Study. Cancers, 15.","DOI":"10.3390\/cancers15041288"},{"key":"ref_31","first-page":"990","article-title":"Conditional Risk and Predictive Factors Associated with Late Toxicity in Patients with Prostate Cancer Treated With External Beam Radiation Therapy Alone in the Randomized Trial RTOG 0126","volume":"120","author":"Alexander","year":"2024","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.ijrobp.2004.07.715","article-title":"Acute and Late Complications After Radiotherapy for Prostate Cancer: Results of a Multicenter Randomized Trial Comparing 68 Gy to 78 Gy","volume":"61","author":"Peeters","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e534","DOI":"10.1016\/S1470-2045(22)00544-7","article-title":"Mechanisms, Mitigation, and Management of Urinary Toxicity from Prostate Radiotherapy","volume":"23","author":"Martin","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/bju.16927","article-title":"Urinary Tract Events After Radical Radiotherapy (RT) for Prostate Cancer According to Pre-RT International Prostate Symptom Score","volume":"137","author":"Zaurito","year":"2026","journal-title":"BJU Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.eururo.2025.07.007","article-title":"Exploring Factors Associated with Late Urinary Toxicity After Prostate Stereotactic Body Radiotherapy: Findings from the PACE-B Study","volume":"89","author":"Ratnakumaran","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.ijrobp.2010.03.040","article-title":"External Beam Radiotherapy for Prostate Cancer: Urinary Outcomes for Men with High International Prostate Symptom Scores (IPSS)","volume":"80","author":"Malik","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/jrr\/rrag012","article-title":"Predictors of Acute Genitourinary Toxicity in Real-Time Image-Gated Spot-Scanning Proton Beam Therapy for Prostate Cancer","volume":"67","author":"Seri","year":"2026","journal-title":"J. Radiat. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/pros.24525","article-title":"Proton Therapy for High-Risk Prostate Cancer: Results from the Proton Collaborative Group PCG 001-09 Prospective Registry Trial","volume":"83","author":"Hasan","year":"2023","journal-title":"Prostate"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ijrobp.2009.11.023","article-title":"The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated with Intensity-Modulated Radiation Therapy","volume":"79","author":"Aizer","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1007\/s00066-024-02343-2","article-title":"Predicting Acute and Late Toxicity in Prostate Cancer Stereotactic Ablative Radiotherapy: The Role of Dosimetric Parameters and Prostate Volume","volume":"201","author":"Ozyigit","year":"2025","journal-title":"Strahlenther. Onkol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijrobp.2007.05.051","article-title":"Toxicity Profile with a Large Prostate Volume After External Beam Radiotherapy for Localized Prostate Cancer","volume":"70","author":"Pinkawa","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lee, B., Lee, R., Benton, J., and Dewar, A. (2025). Clinical Factors Associated with Urinary Morbidity in Men Undergoing Combination Prostate Radiation Therapy. J. Clin. Oncol., 43.","DOI":"10.1200\/JCO.2025.43.16_suppl.e17128"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.clon.2017.03.006","article-title":"Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated with Dose-Escalated Image-Guided Intensity-Modulated Radiotherapy","volume":"29","author":"Byrne","year":"2017","journal-title":"Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Aghdam, N., Pepin, A., Buchberger, D., Hirshberg, J., Lei, S., Ayoob, M., Danner, M., Yung, T., Kumar, D., and Collins, B.T. (2020). Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer in Men with a High Baseline International Prostate Symptom Score (IPSS \u2265 15). Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01060"},{"key":"ref_45","first-page":"165","article-title":"Genitourinary Toxicity in Patients Receiving Transurethral Resection of the Prostate Prior to Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer: A Scoping Review","volume":"42","author":"Neerhut","year":"2024","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/bju.12969","article-title":"Cigarette Smoking During External Beam Radiation Therapy for Prostate Cancer Is Associated with an Increased Risk of Prostate Cancer-Specific Mortality and Treatment-Related Toxicity","volume":"116","author":"Steinberger","year":"2015","journal-title":"BJU Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.clon.2016.04.041","article-title":"Acute and Late Genitourinary Toxicity After 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters","volume":"28","author":"Stankovic","year":"2016","journal-title":"Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.radonc.2015.07.048","article-title":"Multi-Variable Models Predicting Specific Patient-Reported Acute Urinary Symptoms After Radiotherapy for Prostate Cancer: Results of a Cohort Study","volume":"116","author":"Cozzarini","year":"2015","journal-title":"Radiother. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e568","DOI":"10.1016\/S1470-2045(14)70266-9","article-title":"The Biological and Clinical Effects of Smoking by Patients With Cancer and Strategies to Implement Evidence-Based Tobacco Cessation Support","volume":"15","author":"Warren","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_50","unstructured":"National Comprehensive Cancer Network (2026, August 20). NCCN Clinical Practice Guidelines in Oncology: Smoking Cessation. Updated 6 April 2026. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/smoking.pdf."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kopcalic, K., Matic, I.Z., Besu, I., Stankovi\u0107, V., Bukumiri\u0107, Z., Stanojkovi\u0107, T.P., Stepanovi\u0107, A., and Nikitovi\u0107, M. (2022). Circulating Levels of IL-6 and TGF-beta1 in Patients with Prostate Cancer Undergoing Radiotherapy: Associations with Acute Radiotoxicity and Fatigue Symptoms. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10255-6"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Paslaru, A.M., Bounegru, I., Laurentiu, D., and Ciubara, A. (2025). Psychiatric Comorbidity, Functional Status, and Neuroinflammatory Pathways in Cancer Patients with and Without Type 2 Diabetes. Diseases, 13.","DOI":"10.3390\/diseases13100335"},{"key":"ref_53","first-page":"7367","article-title":"Assessment of Risk of Late Rectal Bleeding for Patients with Prostate Cancer Started on Anticoagulation Before or After Radiation Treatment","volume":"34","author":"Schreiber","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ijrobp.2009.02.026","article-title":"External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant Is the Bleeding Toxicity?","volume":"76","author":"Choe","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13014-022-01998-4","article-title":"Patient-Related Risk Factors for Late Rectal Bleeding After Hypofractionated Radiotherapy for Localized Prostate Cancer: A Single-Center Retrospective Study","volume":"17","author":"Kim","year":"2022","journal-title":"Radiat. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ijrobp.2015.12.010","article-title":"Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer","volume":"94","author":"Musunuru","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"22099","DOI":"10.1038\/s41598-023-43202-x","article-title":"Long-Term Findings of Rectal Endoscopy and Rectal Bleeding After Moderately Hypofractionated, Intensity-Modulated Radiotherapy for Prostate Cancer","volume":"13","author":"Bae","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109628","DOI":"10.1016\/j.radonc.2023.109628","article-title":"Validation of Prediction Models for Radiation-Induced Late Rectal Bleeding: Evidence from a Large Pooled Population of Prostate Cancer Patients","volume":"183","author":"Cicchetti","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Schaake, W., van der Schaaf, A., van Dijk, L.V., Bergh, A.C.M.V.D., and Langendijk, J.A. (2018). Development of a Prediction Model for Late Urinary Incontinence, Hematuria, Pain and Voiding Frequency Among Irradiated Prostate Cancer Patients. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197757"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"644","DOI":"10.2340\/1651-226X.2025.42551","article-title":"Risk Factors for Rectal Bleeding in Prostate Cancer After Radiotherapy with a Validation of Current Rectal Dose Constraints","volume":"64","author":"Schaldemose","year":"2025","journal-title":"Acta Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"De Bruyn, P., Klass, M., Van Muylem, A., Jullian, N., Otte, F.-X., Diamand, R., and Preiser, J.-C. (2025). Exploration of Predictive Factors for Acute Radiotherapy-Induced Gastro-Intestinal Symptoms in Prostate Cancer Patients. Cancers, 17.","DOI":"10.3390\/cancers17244035"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3892\/ol.2013.1658","article-title":"Body Mass Index Can Affect Gastrointestinal and Genitourinary Toxicity in Patients with Prostate Cancer Treated with External Beam Radiation Therapy","volume":"7","author":"Doi","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s10147-020-01713-x","article-title":"Predictive Factors of Rectal Hemorrhage in Patients with Localized Prostate Cancer Who Underwent Low-Dose-Rate Brachytherapy","volume":"25","author":"Taniguchi","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ijrobp.2011.08.007","article-title":"Dose-Effect Relationships for Individual Pelvic Floor Muscles and Anorectal Complaints After Prostate Radiotherapy","volume":"83","author":"Smeenk","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1016\/j.ijrobp.2012.03.065","article-title":"Mean Absorbed Dose to the Anal-Sphincter Region and Fecal Leakage Among Irradiated Prostate Cancer Survivors","volume":"84","author":"Alsadius","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Benizri, D., Duchalais-Dassonneville, E., Gautier, M., and Hannoun-Levi, J.M. (2026). Fecal Incontinence After Prostate Cancer Irradiation: A Systematic Literature Review. Prostate Cancer Prostatic Dis.","DOI":"10.1038\/s41391-026-01078-8"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/pros.24852","article-title":"Relationship Between Radiation Therapy and Fecal Incontinence in Patients Treated for Localized Prostate Cancer: Results of the French ICONES Study","volume":"85","author":"Belkacemi","year":"2025","journal-title":"Prostate"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.radonc.2019.12.006","article-title":"Late Toxicity and Quality of Life with Prostate Only or Whole Pelvic Radiation Therapy in High-Risk Prostate Cancer (POP-RT): A Randomised Trial","volume":"145","author":"Murthy","year":"2020","journal-title":"Radiother. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ijrobp.2013.10.042","article-title":"Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer","volume":"88","author":"Ghadjar","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijrobp.2019.01.088","article-title":"Voxel-Based Analysis for Identification of Urethrovesical Subregions Predicting Urinary Toxicity After Prostate Cancer Radiotherapy","volume":"104","author":"Mylona","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ma, C., Hou, Y., Badkul, R., Setianegara, J., Shen, X., Shiao, J., Li, H., and Chen, R.C. (2026). Spatial Dosimetric-Based Prediction of Long-Term Urinary Toxicity After Permanent Prostate Brachytherapy. Cancers, 18.","DOI":"10.3390\/cancers18081287"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijrobp.2021.06.037","article-title":"Radiation Dose to the Intraprostatic Urethra Correlates Strongly with Urinary Toxicity After Prostate Stereotactic Body Radiation Therapy: A Combined Analysis of 23 Prospective Clinical Trials","volume":"112","author":"Leeman","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1016\/j.ijrobp.2009.02.090","article-title":"Radiation Dose-Volume Effects of the Urinary Bladder","volume":"76","author":"Viswanathan","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.radonc.2022.04.022","article-title":"Accumulated Bladder Wall Dose Is Correlated with Patient-Reported Acute Urinary Toxicity in Prostate Cancer Patients Treated with Stereotactic, Daily Adaptive MR-Guided Radiotherapy","volume":"171","author":"Willigenburg","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_75","first-page":"100985","article-title":"Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: The Impact of Daily MRI-Guided Adaptive Radiotherapy on Delivered Dose","volume":"53","author":"Alexander","year":"2025","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"19002","DOI":"10.1038\/s41598-020-75812-0","article-title":"Evaluation of Cytokine Expression and Circulating Immune Cell Subsets as Potential Parameters of Acute Radiation Toxicity in Prostate Cancer Patients","volume":"10","author":"Stanojkovic","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s00066-015-0841-3","article-title":"Early Hematologic Changes During Prostate Cancer Radiotherapy Predictive for Late Urinary and Bowel Toxicity","volume":"191","author":"Pinkawa","year":"2015","journal-title":"Strahlenther. Und Onkol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"D\u2019Auria, F., Valvano, L., Calice, G., D\u2019eSposito, V., Cabaro, S., Formisano, P., Bianchino, G., Traficante, A., Bianculli, A., and Lazzari, G. (2024). Hypofractionated Radiotherapy with Simultaneous Integrated Boost for Localized Prostate Cancer Patients: Effects on Immune System and Prediction of Toxicity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457839"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ijrobp.2022.05.048","article-title":"The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer: A Validation Study from NRG\/RTOG 0521","volume":"114","author":"Hall","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12967-023-03924-y","article-title":"Prognostic Value of the Pretreatment Systemic Immune-Inflammation Index in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"21","author":"Meng","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12957-022-02878-7","article-title":"Prognostic Significance of Pretreatment Systemic Immune-Inflammation Index in Patients with Prostate Cancer: A Meta-Analysis","volume":"21","author":"Zhang","year":"2023","journal-title":"World J. Surg. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s00066-017-1144-7","article-title":"Effects of Definitive and Salvage Radiotherapy on the Distribution of Lymphocyte Subpopulations in Prostate Cancer Patients","volume":"193","author":"Sage","year":"2017","journal-title":"Strahlenther. Onkol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.ijrobp.2014.01.002","article-title":"Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study","volume":"88","author":"Foro","year":"2014","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1016\/j.ijrobp.2008.10.039","article-title":"Radiation-Induced Lymphocyte Apoptosis to Predict Radiation Therapy Late Toxicity in Prostate Cancer Patients","volume":"74","author":"Schnarr","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Al-Hamami, S.S., Kurucz, S., Vondracek, V., Pekar, V., Andrl\u00edk, M., D\u011bde\u010dkov\u00e1, K., Bene\u0161ov\u00e1, I., Haas, A., Ondrov\u00e1, B., and Pasztorov\u00e1, A. (2025). Temporal Dynamics of Lymphocytes in Prostate Cancer Patients Treated with Proton Therapy. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1470876"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/09553002.2026.2630993","article-title":"Dosimetric Correlation of Integral Dose-Dependent Lymphopenia in Bone Marrow After Pelvic Radiotherapy in Locally Advanced Prostate Cancer","volume":"102","author":"Basaran","year":"2026","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"110230","DOI":"10.1016\/j.radonc.2024.110230","article-title":"Pelvic Bone Marrow Dose-Volume Predictors of Late Lymphopenia Following Pelvic Lymph Node Radiation Therapy for Prostate Cancer","volume":"195","author":"Pavarini","year":"2024","journal-title":"Radiother. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Helissey, C., Cavallero, S., Guitard, N., Thery, H., Parnot, C., Schernberg, A., Aissa, I., Raffin, F., Le Coz, C., and Mondot, S. (2024). Correlation Between Electronic Patient-Reported Outcomes and Biological Markers of Key Parameters in Acute Radiation Cystitis Among Patients with Prostate Cancer (RABBIO): Prospective Observational Study. JMIR Cancer, 10.","DOI":"10.2196\/48225"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"217931","DOI":"10.1016\/j.canlet.2025.217931","article-title":"Extracellular Vesicle Proteomics Identify Neutrophils as Potential Mediators of Bladder Radiotoxicity in Prostate Cancer","volume":"631","author":"Molony","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1158\/1078-0432.CCR-25-2102","article-title":"Integration of Dose Surface Maps and Genetic Data Identifies the Lower Posterior Rectum as a Key Region for Toxicity After Prostate Cancer Radiotherapy","volume":"31","author":"Bouzaki","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.radonc.2021.12.040","article-title":"Germline Variants Disrupting microRNAs Predict Long-Term Genitourinary Toxicity After Prostate Cancer Radiation","volume":"167","author":"Kishan","year":"2022","journal-title":"Radiother. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1200\/JCO.2023.41.16_suppl.5089","article-title":"Early Findings From the GARUDA Trial: The Impact of a Genetic Signature of Late Radiation Toxicity on Prostate Cancer Treatment Decision Making","volume":"41","author":"Weidhaas","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1200\/JCO.2026.44.7_suppl.359","article-title":"Germline Radiosensitivity Biomarker for Radiation-Induced GU Toxicity Following Radiation Therapy in Localized Prostate Cancer (GARUDA): Two-Year Outcomes of a Phase II Clinical Trial","volume":"44","author":"Jamshidian","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"21306","DOI":"10.1038\/s41598-022-25328-6","article-title":"Association of Polymorphisms in TGFB1, XRCC1, XRCC3 Genes and CD8 T-Lymphocyte Apoptosis with Adverse Effect of Radiotherapy for Prostate Cancer","volume":"12","author":"Malisic","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ijrobp.2012.02.061","article-title":"Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated with Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGFbeta1 Gene","volume":"85","author":"Ost","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.radonc.2012.10.017","article-title":"Individual Patient Data Meta-Analysis Shows No Association Between the SNP rs1800469 in TGFB1 and Late Radiotherapy Toxicity","volume":"105","author":"Barnett","year":"2012","journal-title":"Radiother. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhu, M.L., Wang, M., Shi, T.Y., Li, Q.-X., Xi, P., Xia, K.-Q., Zheng, L., and Wei, Q.-Y. (2013). No Association Between TGFB1 Polymorphisms and Late Radiotherapy Toxicity: A Meta-Analysis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076964"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1080\/09553002.2025.2459079","article-title":"Single Nucleotide Polymorphisms in the RNASEL Gene Are Associated with Acute and Late Adverse Effects of Radiotherapy and Fatigue in Patients with Prostate Adenocarcinoma","volume":"101","author":"Petrovic","year":"2025","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1158\/1078-0432.CCR-12-2718","article-title":"A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome After Radiation Therapy for Localized Prostate Cancer","volume":"19","author":"Schoenfeld","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Guhlich, M., Hubert, L., Mergler, C.P.N., Rave-Fraenk, M., Dr\u00f6ge, L.H., Leu, M., Schmidberger, H., Rieken, S., Hille, A., and Schirmer, M.A. (2021). Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1. Cancers, 13.","DOI":"10.3390\/cancers13215585"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13148-025-01846-8","article-title":"Epigenome-Wide Analysis Reveals Potential Biomarkers for Radiation-Induced Toxicity Risk in Prostate Cancer","volume":"17","author":"Peleteiro","year":"2025","journal-title":"Clin. Epigenet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.radonc.2021.03.024","article-title":"Development of a Method for Generating SNP Interaction-Aware Polygenic Risk Scores for Radiotherapy Toxicity","volume":"159","author":"Franco","year":"2021","journal-title":"Radiother. Oncol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:31:32Z","timestamp":1789129892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/9\/1477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":102,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["life16091477"],"URL":"https:\/\/doi.org\/10.3390\/life16091477","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}