Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.

OBJECTIVE To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. MATERIALS AND METHODS In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6-12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. RESULTS 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). CONCLUSION Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours

Focal High Intensity Focused Ultrasound in the Treatment of Non-Metastatic Prostate Cancer

Introduction This thesis will explore the adverse events, side-­‐effect profile and efficacy of high intensity focused ultrasound to treat non-­‐metastatic prostate cancer. I will look at the background of prostate cancer and how advances in the diagnostic pathway for prostate cancer, as well as the paradigm shifts in treatment for this disease, have defined the current treatment landscape for localized prostate cancer and how focal therapy fits in. Objectives The aim of this thesis is to evaluate the efficacy and medium-­‐term outcomes of focal HIFU from a multicentre registry of over 600 cases treated over the last 10 years in the UK. In so doing, this thesis will explore the use of registries in defining novel treatments as a useful body of evidence that might be used to impact on standard care in the absence of randomized controlled studies which are difficult to conduct within surgical specialties. The future role of focal therapy and high intensity focused ultrasound will be discussed, providing insights into the evolution of this ablative therapy, and how it might take its place within the armamentarium of treatments available for localized prostate cancer. Results The multicenter academic focal HIFU registry demonstrates acceptable oncological control in men diagnosed with non-­‐metastatic prostate cancer is achievable with acceptable o Conclusions The medium-­‐term data presented in this thesis is the first of its kind and supports the contention that focal therapy has a role in decreasing the genito-­‐urinary side-­‐effects associated with standard whole-­‐gland therapies. Trifecta status of leak-­‐free, pad-­‐free continence, erections sufficient for intercourse, and oncological control is achievable with focal HIFU with acceptable results. Ultimately, long-­‐term data will be necessary, including 5 research into comparative effectiveness to further establish the future role of focal therapy in treating localized prostate cancer

Radiotherapy is associated with reduced continence outcomes following implantation of the artificial urinary sphincter in men with post-radical prostatectomy incontinence

Objectives: The objective of this study is to present the outcomes of men undergoing implantation of artificial urinary sphincter, after treatment for prostate cancer and also to determine the effect of radiotherapy on continence outcomes after artificial urinary sphincter (AUS) implantation. Material and Methods: A prospectively acquired database of all 184 patients having AUS insertion between 2002 and 2012 was reviewed, and demographic data, mode of prostate cancer treatment(s) before implantation, and outcome in terms of complete continence (pad free, leak free) were assessed. Statistical analysis was performed by Chi-squared and Fisher's exact tests. Results: A total of 58 (32%) men had bulbar AUS for urodynamically proven stress urinary incontinence consequent to treatment for prostate cancer in this period. Median follow-up post-AUS activation was 19 months (1–119). Forty-eight (83%) men had primary AUS insertion. Twenty-one (36%) men had radiotherapy as part of or as their sole treatment. Success rates were significantly higher in nonirradiated men having primary sphincter (89%) than in irradiated men (56%). Success rates were worse for men having revision AUS (40%), especially in irradiated men (33%). Conclusion: Radiotherapy as a treatment for prostate cancer was associated with significantly lower complete continence rates following AUS implantation

An exploratory study of dose escalation versus standard focal High Intensity Focused Ultrasound for treating non-metastatic prostate cancer.

Objective To compare cancer control rates of standard compared to dose escalation focal high-intensity focused ultrasound (HIFU) of prostate cancer. Materials and methods A prospectively maintained HIFU (Sonablate® 500) database identified 598 patients were identified who underwent focal HIFU (Sonablate® 500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year. Thereafter, PSA was measured 6-monthly. mpMRI with biopsy was used for MRI-suspicion of recurrence. Treatments were delivered in a quadrant or hemiablation fashion depending on the gland volume as well as tumour volume and location. Prior to mid-2015, standard focal-HIFU was used (two HIFU blocks); after this date some urologists conducted dose escalation focal-HIFU (3 overlapping HIFU blocks). Propensity matching was used to ensure two matched groups leading to 162 cases for this analysis. Treatment failure was defined by any secondary treatment (systemic therapy, cryotherapy, radiotherapy, prostatectomy, or further HIFU), metastasis from prostate cancer without further treatment, tumour recurrence with Gleason score >/=7 (>/=3+4) on prostate biopsy without further treatment, or prostate cancer-related mortality. Complications and side-effects were also compared. Results Median age was 64.5 years (IQR 60-73.5) in the standard focal-HIFU group and 64.5 years (IQR 60-69) in the dose-escalation group. Median prostate volume was 37ml (IQR 17-103) in standard group and 47.5ml (IQR 19-121) in the dose-escalation group. As tumour volume on mpMRI and Gleason score were major matching criteria these were identical with 0.43ml (IQR 0.05-2.5) and Gleason 3+3=6 in 1/32 (3%), 3+4=7 in 27/32 (84%), and 4+3=7 in 4/32 (13%). Recurrence in treated areas were found in 10/32 (31%) when standard treatment zones were applied, and in 6/32 (19%) of dose-escalation focal-HIFU (p=0.007). Conclusion This exploratory study shows that dose escalation focal-HIFU may achieve higher rates of disease control compared to standard focal-HIFU. Further prospective comparative studies are needed

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET):A Systematic Review and International Consensus Recommendations

Background and objective: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. Methods:A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. Key findings and limitations: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. Conclusions and clinical implications: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. Patient summary:Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.</p

Cancer control outcomes following focal therapy using high-intensity focused ultrasound in 1379 men with nonmetastatic prostate cancer: a multi-institute 15-year experience

Background: local therapy aims to treat areas of cancer to confer oncological control whilst reducing treatment-related functional detriment.Objective: to report oncological outcomes and adverse events following focal high-intensity focused ultrasound (HIFU) for treating nonmetastatic prostate cancer.Design, setting, participants: an analysis of 1379 patients with ≥6 mo of follow-up prospectively recorded in the HIFU Evaluation and Assessment of Treatment (HEAT) registry from 13 UK centres (2005-2020) was conducted. Five or more years of follow-up was available for 325 (24%) patients. Focal HIFU therapy used a transrectal ultrasound-guided device (Sonablate; Sonacare Inc., Charlotte, NC, USA).Outcome measurements and statistical analysis: failure-free survival (FFS) was primarily defined as avoidance of no evidence of disease to require salvage whole-gland or systemic treatment, or metastases or prostate cancer-specific mortality. Differences in FFS between D'Amico risk groups were determined using a log-rank analysis. Adverse events were reported using Clavien-Dindo classification.Results and limitations: the median (interquartile range) age was 66 (60-71) yr and prostate-specific antigen was 6.9 (4.9-9.4) ng/ml with D'Amico intermediate risk in 65% (896/1379) and high risk in 28% (386/1379). The overall median follow-up was 32 (17-58) mo; for those with ≥5 yr of follow-up, it was 82 (72-94). A total of 252 patients had repeat focal treatment due to residual or recurrent cancer; overall 92 patients required salvage whole-gland treatment. Kaplan-Meier 7-yr FFS was 69% (64-74%). Seven-year FFS in intermediate- and high-risk cancers was 68% (95% confidence interval [CI] 62-75%) and 65% (95% CI 56-74%; p = 0.3). Clavien-Dindo &gt;2 adverse events occurred in 0.5% (7/1379). The median 10-yr follow-up is lacking.Conclusions: focal HIFU in carefully selected patients with clinically significant prostate cancer, with six and three of ten patients having, respectively, intermediate- and high-risk cancer, has good cancer control in the medium term.PATIENT SUMMARY: Focal high-intensity focused ultrasound treatment to areas of prostate with cancer can provide an alternative to treating the whole prostate. This treatment modality has good medium-term cancer control over 7 yr, although 10-yr data are not yet available.</p

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA  335 radical prostatectomy and 501 focal therapy patients were eligible for matching. For focal therapy, 420 had HIFU and 81 cryotherapy. Cryotherapy was used predominantly for anterior cancer. After matching, 246 RP and 246 FT cases were identified. For radical prostatectomy, mean (SD) age was 63.4 (5.6) years, median (IQR) PSA 7.9 g/ml (6-10) and median (IQR) follow-up 64 (30-89) months. For focal therapy, these were 63.3 (6.9) years, 7.9 ng/ml (5.5-10.6) and 49 [34-67] months, respectively. At 3, 5 and 8 years, FFS (95%CI) was 86% (81-91%), 82% (77-88%) and 79% (73-86%) for radical prostatectomy compared to 91% (87-95%), 86% (81-92%) and 83% (76-90%) following focal therapy (p = 0.12). In patients with non-metastatic low- intermediate prostate cancer, oncological outcomes over 8 years were similar between focal therapy and radical prostatectomy

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study

Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA  335 radical prostatectomy and 501 focal therapy patients were eligible for matching. For focal therapy, 420 had HIFU and 81 cryotherapy. Cryotherapy was used predominantly for anterior cancer. After matching, 246 RP and 246 FT cases were identified. For radical prostatectomy, mean (SD) age was 63.4 (5.6) years, median (IQR) PSA 7.9 g/ml (6-10) and median (IQR) follow-up 64 (30-89) months. For focal therapy, these were 63.3 (6.9) years, 7.9 ng/ml (5.5-10.6) and 49 [34-67] months, respectively. At 3, 5 and 8 years, FFS (95%CI) was 86% (81-91%), 82% (77-88%) and 79% (73-86%) for radical prostatectomy compared to 91% (87-95%), 86% (81-92%) and 83% (76-90%) following focal therapy (p = 0.12). In patients with non-metastatic low- intermediate prostate cancer, oncological outcomes over 8 years were similar between focal therapy and radical prostatectomy