BackgroundRadiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy.Patients and methodsA bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS).ResultsGene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients [HR = 3.21 (1.35–7.67); P = 0.003]. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases [HR = 2.71 (1.11–6.63); P = 0.030]. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) [HR = 3.23 (1.22–8.59); P = 0.019] whilst CAPRA itself was not significant [HR = 1.88, (0.52–6.77); P = 0.332]. A high concordance [100% (61.5–100)] for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance.ConclusionsThe Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.

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Objective: Consistency in target organ and organ at risk position from planning to treatment is an important basic principle of radiotherapy. This study evaluates the effectiveness of bladder-filling instructions in achieving a consistent and reproducible bladder volume at the time of planning CT and daily during the course of radical radiotherapy for prostate cancer. It also assessed the rate of bladder filling before and at the end of radiotherapy. Methods: 30 men attending for radiation therapy planning for prostate cancer received written and verbal bladder-filling instructions. They had their bladder volume assessed using a bladder ultrasound scanner post-void, immediately prior to planning CT scan and then daily immediately prior to treatment while in the therapy position. The inflow was calculated using the void and full bladder volumes and the time for the bladder to fill. Results: The mean bladder volume at the time of planning was 282 ml (range 89-608 ml, standard deviation (SD)5144.5 ml). This fell during treatment, with a mean value for all treatments of 189 ml (range 11-781 ml, SD5134 ml). During radiotherapy, 76% (828/1090), 53% (579/1090) and 36% (393/1090) of bladder volumes had .50 ml, .100 ml and .150 ml difference, respectively when compared with their volume at the time of planning. Inflow reduced from 4.6 ml min -1 , SD52.9 min -1 at planning to 2.5 min -1 , SD51.8 min -1 after radiotherapy. Conclusion: The Bladderscan device (BVI 6400 Bladderscan, Verathon Medical UK, Sandford, UK) provides an effective means of assessing bladder volume prior to radiotherapy for prostate cancer. The evaluated bladder-filling protocol does not produce consistent, reproducible bladder volumes for radiotherapy. Reproducibility of target volume position is a fundamental component of external beam radiotherapy at any site, but is of particular importance where a doseescalated regimen is being employed and where the surrounding organs are both dose and volume sensitive. For men receiving dose-escalated radical prostate radiotherapy, a consistent bladder volume between planning and treatment is vital. Although there are differing opinions on the influence of bladder volume on interfraction prostate position [1][2][3][4][5][6][7], the influence of the irradiated bladder volume on acute and late urinary [8] and bowel toxicity [2,9] has been well documented.Despite the apparent importance of controlling bladder volume for prostate radiotherapy, there is surprisingly limited research into the provision of bladder-filling instructions that produce acceptable dose-volume histograms (DVHs) and provide a reproducible bladder volume from planning through to treatment [1-2, 10, 11] rather than an unreliable and misleading snapshot at the time of planning.This study was designed to first validate bladder volume measurements using a non-invasive transabdominal bladder ultrasound device (BVI 6400 Bladderscan, Verathon Medical UK, Sandford, UK) before using it to evaluate the effectiveness of standardised bladder-filling instru...

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