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    Interventional procedure overview of focal therapy using high-intensity focused ultrasound for localised prostate cancer

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    Efficacy summary

    Note: there was substantial overlap in the studies included in the systematic reviews, refer to List of studies included in the IP overview for more information.

    Oncological outcomes

    Cancer control outcomes

    Overall survival

    In an analysis of a prospective registry of 1,379 people, overall survival (OS) at 7 years was 97% (95% confidence interval [CI] 96% to 99%; Reddy 2022).

    A propensity score weighted analysis compared 530 people who had focal therapy (including 419 who had focal HIFU) to 830 people who had radical therapy (including EBRT and prostatectomy; van Son 2021). The following outcomes were reported:

    • Two-way analysis (focal compared with radical therapy):

      • People treated with focal therapy had statistically significantly higher OS at 6 years than people treated with radical therapy (97.5% compared with 93.4%, p=0.02; Kaplan–Meier analysis).

      • There were no statistically significant differences between the groups in overall mortality (p>0.05; regression analysis).

    • Three-way analysis (focal therapy compared with radical prostatectomy compared with radical EBRT):

      • Overall mortality was statistically significantly less likely in the focal therapy group than the EBRT group (hazard ratio [HR] 0.29, 95% CI 0.11 to 0.76, p=0.008; regression analysis).

      • There was no statistically significant difference in overall mortality between the focal therapy and radical prostatectomy groups.

    In a retrospective case series of 1,032 people, OS at 96 months was 96.6% (Stabile 2019).

    Failure-free survival

    In the analysis of a prospective registry of 1,379 people, failure-free survival (FFS) at 7 years was 69% (95% CI 64% to 74%; Reddy 2022). Failure was defined as evidence of cancer requiring whole-gland salvage treatment or 3rd focal treatment (2 were permitted in the protocol), systemic treatment, development of prostate cancer metastases, or prostate cancer-specific death. By D'Amico risk class, FFS at 7 years was:

    • Low risk cancers 88% (95% CI 77% to 99%)

    • Intermediate risk cancers 68% (95% CI 62% to 75%)

    • High risk cancers 65% (95% CI 56% to 74%).

    The propensity score weighted analysis compared 530 people who had focal therapy (including 419 who had focal HIFU) to 830 people who had radical therapy (including EBRT and prostatectomy; van Son 2021). FFS was a composite endpoint of need for local salvage treatment, development of metastatic disease, use of systemic treatment (ADT or chemotherapy) or progression to a watchful waiting strategy. The following outcomes were reported:

    • Two-way analysis (focal compared with radical therapy):

      • There was no statistically significant difference in FFS at 6 years between focal and radical therapy groups (p=0.10; Kaplan–Meier analysis).

      • There was no statistically significant difference between the groups in treatment failure (p>0.05; regression analysis).

    • Three-way analysis (focal therapy compared with radical prostatectomy compared with radical EBRT):

      • Treatment failure was statistically significantly more likely in both focal therapy and radical prostatectomy groups compared to EBRT (HR 2.24 [95% CI 1.4 to 3.64] and HR 2.41 [95% CI 1.44 to 4.05]; both p<0.001; regression analysis).

    In the retrospective case series of 1,032 people, biopsy FFS at 96 months was 54.0%. Biopsy FFS was defined as the presence of clinically significant prostate cancer at post-treatment biopsy (Stabile 2019).

    Recurrence

    In a systematic review of 20 studies, 9 studies reported that clinically significant infield recurrence was detected in 5% to 22% of people over median follow up ranging from 6 to 56 months. Seven studies reported that any prostate cancer (clinically significant or not) in the HIFU field was detected in 10% to 37% of people over median follow up ranging from 12 to 56 months. Furthermore, 7 studies reported that clinically significant out-of-field progression was detected in 2% to 29% of people over median follow up ranging from 6 to 33 months. Six studies reported that any prostate cancer (clinically significant or not) out of the HIFU field was detected in 8% to 35% of people over median follow up ranging from 12 to 56 months (Bakavicius 2022).

    A retrospective cohort study compared 152 people who had focal HIFU to 54 people who had whole-gland HIFU. At 12 months follow up, outcomes were available for 59 partial-gland people and 27 whole-gland people. There was no statistically significant difference in the proportion of people in each group who had any positive biopsy (partial-gland 27.1% compared with whole-gland 29.6%, p=0.713; Byun 2022).

    Metastasis

    In a systematic review of 3 studies on focal HIFU as a salvage treatment, postoperative metastasis rates ranged from 5% to 12.5% over a median follow up ranging from 16.3 to 35 months (Khoo 2020).

    In the analysis of a prospective registry of 1,379 people, metastasis-free survival at 7 years was 100% (95% CI 99% to 100%; Reddy 2022).

    PSA outcomes

    In the systematic review of 20 studies, 10 studies reported that the median PSA reduction was 53% to 84%. Six studies reported that the median time to reach PSA nadir ranged from 3 to 12 months after surgery (Bakavicius 2022).

    In the systematic review of 3 studies on focal HIFU as a salvage treatment, biochemical disease-free survival (BDFS) was defined as a rise of 2 ng/mL or more above the PSA nadir level (Khoo 2020). In the 3 studies, BDFS ranged from 0% to 67% over follow up ranging from 16.3 to 35 months.

    Retreatments

    In the systematic review of 20 studies, 13 studies reported details of retreatments. These included (Bakavicius 2022):

    • Further focal HIFU:

      • In-field recurrence: 5% to 11% of people had a second focal HIFU (2 studies).

      • Out-of-field progression: 2% to 13% of people had a second focal HIFU (4 studies).

      • Not specified disease location: 4% to 19% of people had a second focal HIFU (7 studies).

    • Other retreatments:

      • Salvage focal cryotherapy: 1% of people (1 study).

      • Salvage whole-gland HIFU: 0.4% to 10% of people (3 studies).

      • Salvage radical prostatectomy: 1% to 22% of people (10 studies).

      • Salvage EBRT with or without ADT: 0.9% to 8% of people (9 studies).

      • ADT only: 0.2% to 6% of people (6 studies).

    In the systematic review of 3 studies on focal HIFU as a salvage treatment, 1 study reported that 8% of people converted to second-line therapy (Khoo 2020).

    In the analysis of a prospective registry of 1,379 people, salvage whole-gland or systemic treatment-free survival at 7 years was 75% (95% CI 71% to 80%; Reddy 2022).

    In the retrospective case series of 1,032 people, retreatment-free survival was 45.8% and radical treatment-free survival was 80.8% at 96 months after surgery. Radical treatment-free survival was defined as radical prostatectomy, EBRT and other whole-gland therapies (Stabile 2019). Throughout the follow-up period, 271 people were retreated (26.3%). Retreatments included:

    • Focal HIFU, n=193

    • Focal cryotherapy, n=12

    • EBRT, n= 9

    • Radical prostatectomy, n=30

    • Whole-gland HIFU, n=4

    • ADT, n=20

    • Other, n=3.

    Quality of life

    In the systematic review of 20 studies, 2 studies reported no deterioration in QoL on the FACT-P questionnaire (Bakavicius 2022).