Abstract

ObjectivesFocal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes. MethodsA retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2‐weighted, diffusion‐weighted and dynamic contrast‐enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer‐specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression. ResultsMedian age at focal salvage HIFU was 71 years (interquartile range [IQR] 65–74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8–24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor. ConclusionsOne pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required.

Highlights

  • Focal salvage HIFU is used in some centers as it may offer disease control in men at high risk of progression whilst minimizing complications compared to salvage prostatectomy [2,3] recent publications suggest that with a robotic approach the complications are lower than previously reported [4,5]

  • Our study evaluated whether mpMRI pharmacokinetic quantitative parameters can predict failure in patients undergoing salvage HIFU treatment for radioreccurent PCa

  • Our results show that the extracellular space of the tumor, represented by Ve value, measured in the dynamic contrast-enhanced (DCE) sequence of the mpMRI, is an independent predictor of failure, corrected for well-known clinical parameters associated with treatment failure

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Summary

Introduction

Focal salvage HIFU is used in some centers as it may offer disease control in men at high risk of progression whilst minimizing complications compared to salvage prostatectomy [2,3] recent publications suggest that with a robotic approach the complications are lower than previously reported [4,5]. Focal salvage therapy aims to treat the area of recurrent disease rather than the entire prostate gland. A recent publication on outcomes of salvage HIFU after external beam radiotherapy (EBRT) failure have shown low risk of urinary incontinence, erectile dysfunction and rectal injury [2]. About a half of patients can have biochemical failure after focal salvage treatment

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