Risk stratification in the management of localised prostate cancer treated with radical radiotherapy

At a population level, improved patient selection using novel prognostic or predictive biomarkers will allow greater individualisation of treatment for men with localised prostate cancer. At an individual level, advances in radiotherapy will enable more precise and accurate tumour targeting improving the therapeutic ratio. <br><br>A large clinically annotated database of Northern Irish men treated with radical radiotherapy for localised prostate cancer was generated which served as a resource to facilitate biomarker investigation in multiple settings.

Whole-transcriptome analysis of diagnostic prostate tissue was carried out and a novel 70-gene Metastatic Assay, that had previously proven prognostic for biochemical failure-free and metastasis-free survival in surgical patients was, for the first time, shown to be prognostic for the same outcomes in men treated with radical radiotherapy. Neither pre-radiotherapy PSA nadir nor neutrophil-lymphocyte ratio, both clinical biomarkers which had previously shown promise, were found to be prognostic for any outcome of interest in this patient group.

The choice of androgen deprivation therapy subtype was prognostic for biochemical failure, with poorer outcomes in the group treated with anti-androgen monotherapy, but, interestingly, was not prognostic for metastatic disease, prostate-cancer specific survival or overall survival. <br><br>The SPORT High-Risk Trial, a randomised feasibility study designed to investigate the addition of elective pelvic nodal stereotactic radiotherapy (SABR) to prostate SABR in men with unfavourable intermediate- and high-risk localised prostate cancer, was designed and developed as part of this work.

The development of a novel composite volume margin derivation approach is presented here. This method permits the derivation of planning margins for two or more separate CTVs treated using a single isocentre, independent of the assumptions of conventional margin recipes, and was undertaken to provide necessary planning data prior to the opening of the SPORT trial. Early results from this trial are also reported here and, to date, do not demonstrate any evidence of excessive or unexpected toxicity. <br><br>The management of prostate cancer is evolving more rapidly than ever before; the continued development of precision medicine – in all its aspects – is essential to truly allow individualisation of treatment at all stages.<br><br>