Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

Rakauskas, Arnas; Shah, Taimur T.; Peters, Max; Randeva, Jagpal; Hosking‐Jervis, Feargus; Schmainda, Michael; Orczyck, Clement; Emberton, Mark; Arya, Manit; Moore, Caroline M.; Ahmed, Hashim U.

doi:10.1016/j.urolonc.2021.04.017

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…For example, higher Prostate Imaging‐Reporting and Data System (PI‐RADS) score in the primary setting is associated with biochemical failure and metastases by 7 years post‐RT [22]. Other radiomic parameters may also be important; our group previously evaluated preoperative mpMRI pharmacokinetic quantitative variables [23]. After adjustment for seven factors, the median interstitial space volume independently predicted failure after salvage focal HIFU.…”

Section: Discussionmentioning

confidence: 99%

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

et al. 2023

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ObjectivesTo externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.Patients and methodsPatients with biopsy‐confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014–2018; six centres), and from the high‐intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK‐based registries (2006–2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post‐salvage with discrimination (concordance index [C‐index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically‐reasonable risk threshold ranges of 0.14–0.52 and 0.26–0.36 were considered, corresponding to previously published pooled 2‐year recurrence‐free survival rates for salvage local treatments.ResultsA total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow‐ups, and 72/168 (43%) within 2 years. The C‐index was 0.65 (95% confidence interval 0.58–0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a ‘treat all’ strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14–0.52 risk threshold range, and all of the 0.26–0.36 range.ConclusionIn external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow‐up is recommended.

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Section: Discussionmentioning

confidence: 99%

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

et al. 2023

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“…Most studies use ASTRO’s Phoenix criteria to define biochemical failure post HIFU. The Stuttgart definition of biochemical failure (PSA nadir + 1.2 ng/mL) is an additional predictor of clinical failure that can be used in the post-HIFU setting ( 15 , 20 ). Few consensus recommendations include biopsies, PSA and multiparametric MRI for post-HIFU failure detection ( 21 , 22 ).…”

Section: Discussionmentioning

confidence: 99%

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience

Lalla

Elakshar²,

Anidjar³

et al. 2022

Front. Oncol.

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Purpose/objectivesHigh-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure.Materials/methodsWe conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis.ResultsFrom 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%.ConclusionsTo our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.

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“…It was initially assumed that poorer outcome was due to vascularity in T2 hyperintense fibroids ( 10 ) but more recently this phenomenon has been linked to increased amounts of extracellular water: shorter T2 and lower ADC values and thus more densely cellular fibroids have a better outcome ( 11 , 12 ). This is echoed by data from a registry study in radio-recurrent prostate cancer, where the extracellular volume fraction in a multivariate analysis was shown to be the only independent predictor of poor progression-free survival ( 13 ). In brain tissue, where extracellular volume fraction differs between grey and white matter, thermal responses between them have been shown to differ in ex vivo data: the attenuation coefficient curves of white matter show a definite linear behavior in relation to temperature ( 14 ).…”

Section: Vascular and Non-vascular Soft Tissuesmentioning

confidence: 99%

Tissue specific considerations in implementing high intensity focussed ultrasound under magnetic resonance imaging guidance

et al. 2022

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High-intensity focused ultrasound can ablate a target permanently, leaving tissues through which it passes thermally unaffected. When delivered under magnetic resonance (MR) imaging guidance, the change in tissue relaxivity on heating is used to monitor the temperatures achieved. Different tissue types in the pre-focal beam path result in energy loss defined by their individual attenuation coefficients. Furthermore, at interfaces with different acoustic impedances the beam will be both reflected and refracted, changing the position of the focus. For complex interfaces this effect is exacerbated. Moreover, blood vessels proximal to the focal region can dissipate heat, altering the expected region of damage. In the target volume, the temperature distribution depends on the thermal conductivity (or diffusivity) of the tissue and its heat capacity. These are different for vascular tissues, water and fat containing tissues and bone. Therefore, documenting the characteristics of the pre-focal and target tissues is critical for effective delivery of HIFU. MR imaging provides excellent anatomic detail and characterization of soft tissue components. It is an ideal modality for real-time planning and monitoring of HIFU ablation, and provides non-invasive temperature maps. Clinical applications involve soft-tissue (abdomino-pelvic applications) or bone (brain applications) pre-focally and at the target (soft-tissue tumors and bone metastases respectively). This article addresses the technical difficulties of delivering HIFU effectively when vascular tissues, densely cellular tissues, fat or bone are traversed pre-focally, and the clinical applications that target these tissues. The strengths and limitations of MR techniques used for monitoring ablation in these tissues are also discussed.

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Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

Abstract: Highlight Quantitative mpMRI parameters predict failure of salvage HIFU in radiorecurrent prostate cancer Tumour microenvironment might produce heat-sinks which counter the effect of HIFU Ve value measured in the DCE sequence of the mpMRI is an independent predictor of treatment failure

Cited by 5 publications

References 17 publications

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience

Tissue specific considerations in implementing high intensity focussed ultrasound under magnetic resonance imaging guidance

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