Immunological factors underlying radiation-induced toxicity in prostate cancer patients: a systematic review

Radiotherapy (RT) represents a well-established treatment modality for patients diagnosed with prostate cancer. Despite a low toxicity profile, a small proportion of patients suffer long-term effects with a decrease in quality of life. Several risk factors for the prediction of radiation-induced toxicity have been evaluated. This study aimed to systematically review the current literature on the immunological factors underlying radiation-induced toxicity in prostate cancer patients undergoing RT.

A comprehensive search in three databases (PubMed, Web of Science, Scopus) was conducted. Eligible papers reported on toxicity and immunological factors in patients treated with RT with curative intent. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in each step. The quality of the included articles was assessed utilizing the Newcastle Ottawa Quality Assessment Scale (NOS).

A total of 15 studies, encompassing 1237 patients, were included, with a median age ranging from 62 to 74 years. Ten studies reported on primary RT only, while five assessed both primary and postoperative RT. Tumor stage and lymph node involvement varied among studies. Utilized radiation treatment modalities were intensity-modulated radiotherapy, stereotactic body radiotherapy, three-dimensional conventional radiotherapy, and low-dose rate brachytherapy. Androgen deprivation therapy was administered and reported inconsistently. Immunological factors and assessed toxicities varied between studies. Thus, reports on immunological factors and predictive biomarkers remain scarce and inconclusive. Besides lymphocyte counts, the most common molecules that significantly correlated with RT-induced toxicity in prostate cancer patients were interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1).

Publications on immunological factors as predictors of RT-induced toxicity remain rare and exhibit a high degree of variability in treatment, toxicity, and immunological factor assessment. Yet, IL-6, IL-2, TNF-α, and lymphocyte counts are the most consistent markers for predicting toxicity in prostate cancers post-RT. Future preclinical and clinical studies should corroborate these findings, with the final goal of improving patient treatment outcomes.