Acute epithelial toxicity is prognostic for improved prostate cancer response to radiotherapy: a retrospective multi-centre cohort study

Publication date: Available online 11 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas Eade, Ananya Choudhury, Alan Pollack, Matthew Abramowitz, Felix M. Chinea, Linxin Guo, Jason Kennedy, Sandra Louw, George Hruby, Andrew Kneebone, Catharine West
IntroductionPatients with germline mutations in their DNA repair pathway are at risk of increased toxicity from radiotherapy. These patients could also have radiosensitive cancer cells. We hypothesised that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity.Methods and MaterialsThe study design was retrospective with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiotherapy with curative intent and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis or mucus) were related to freedom from late biochemical failure (FFBF; nadir+2). The validation cohort were from two separate institutions.Results503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage, had a longer FFBF on both univariate (HR 0.37; p=0.004) and multivariate (HR 0.45; p=0.035) analysis. The impact of acute toxicity on late FFBF appeared to be greater in patients treated with androgen deprivation (HR 0.19) than those without (HR 0.48).ConclusionPatients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiotherapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity.

Teaser

We hypothesised that increased early radiation toxicity, measured using specific subdomains, is associated with improved local control following prostate radiotherapy. We used a discovery cohort to select the specific subdomains of acute GU and GI toxicity most likely to represent epithelial damage, and subsequently confirmed in patients from 2 other institutions that acute toxicity significantly reduces late biochemical failure. This confirms there is a potential genetic link between acute radiation toxicity and cancer outcomes.


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