Ki67 is an independent predictor of recurrence in the largest randomised trial of 3 radiation fractionation schedules in localised prostate cancer

Publication date: Available online 3 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Anna C. Wilkins, Barry Gusterson, Zsolt Szijgyarto, Joanne Haviland, Clare Griffin, Christine Stuttle, Frances Daley, Catherine M. Corbishley, David P. Dearnaley, Emma Hall, Navita Somaiah
BackgroundExternal beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could improve treatment stratification. This study assessed if the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiotherapy fractionation in patients participating in ", a randomised trial of three radiotherapy fractionation schedules (74Gy/37f vs 60Gy/20f vs 57Gy/19f).MethodsA matched case:control study design was used, patients with biochemical/clinical failure >2 years after radiotherapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, PSA, tumour-stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker-fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.ResultsUsing 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (IQR:3.9-9.8) and 11.0% (IQR:7.0-15.0) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR was estimated to increase by 9% per 1% increase in mean Ki67 score (OR=1.09, 95%CI:1.04–1.15,p=0.001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.ConclusionsDiagnostic Ki67 did not predict BCR according to fractionation schedule in ", however it was a strong independent prognostic factor for BCR.



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