BERKELEY, CA (UroToday.com) - In February 2013 we published data, in the Journal of Urology, on 10-year cancer-specific survival and metastasis-free survival following high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer. The data were collected over a period of 15 years. It is a rarity to see such long-term results published for any definitive local therapy for prostate cancer, let alone an emerging technology. Cryoablation, by contrast, preceded HIFU by 10 years, but 10-year cancer-specific survival or freedom from metastasis rates have yet to be published. The significance and reproducibility of our long-term HIFU results in localized prostate cancer was confirmed by the publications of other groups.
Ganzer et al. (2013) reported a retrospective single-center study of 538 consecutive patients in the British Journal of Urology International.[1] Efficacy was evaluated with overall, metastatic-free, and prostate cancer-specific survival rates. Morbidity was also assessed. Per D’Amico stratification, the population included 229 and 211 men with low- and moderate-risk disease characteristics, respectively. On average, 1.22 HIFU sessions were performed per patient. Ten-year cancer-specific survival rates for patients were 100% and 96.2%, and the metastatic free rate at 10 years was 99.6% and 94.3% for the low- and intermediate-risk groups, respectively. No fistulas were observed following first HIFU and 4 (0.7%) were observed following repeat HIFU. Post treatment, UTI was observed in 10%, and 28.3% of patients had an episode of bladder outlet obstruction. At most recent follow up, grade I incontinence (defined as loss of urine under heavy exercise requiring 0 to 1 pad per day) was observed in 14% of subjects and grade II and III was reported by 2.4% and 0.7% of patients, respectively. Potency was assessed 12 months following HIFU. Of those men potent prior to treatment, 25% were considered potent without the use of any medical assistance including pharmaceutical assistance with PDE-5 inhibitors such as sildenafil citrate (Viagra). Additionally, 40% were potent with medical assistance. This yields a return to intercourse rate of 65% at 12 months. Note, the North American standard potency reporting lists patients potent, with or without oral pharmaceutical assistance.
We also reported the long-term cancer control and morbidity of HIFU. We included primary HIFU patients with localized disease (T1-2, N0, M0, PSA < 50 ng/ml). Those with follow up < 15 months, previous long-term ADT, locally advanced PCa, or any PSA-influencing therapy were excluded. All patients underwent whole gland HIFU. Of 704 study patients, 78.5% had intermediate- or high-risk disease. Follow up was up to 14 years. Ten-year cancer-specific survival was 99%, metastasis-free survival 95%, and 10-year salvage treatment-free rates were 98% in low-risk, 72% in intermediate-risk, and 68% in high-risk patients. Side effects showed to be moderate. Morbidity was assessed and stratified according to the generation of device used: prototype (cohort 1), Maxis – the first commercially available device launched in 2000 (cohort 2) and the Ablatherm Integrated Imaging available in 2005 (cohort 3). The rates of short-intermediate term morbidity included incontinence (4%), obstruction (4.6%), infection (2.1%), recto-urethral fistula formation (0.23%), perineal pain (0.7%), and other morbidity (4.4%). There were no cases of fistula since the introduction of Ablatherm Integrated Imaging in 2005. The morbidity profile, but not the overall rate, changed significantly in subsequent cohorts: The overall rate of urinary incontinence (grade II or III) > 3 months was 3.26%, with rates of 5.1%, 3.1%, and 1.5% in Cohorts 1, 2, and 3, respectively. The overall rate of secondary obstruction (from necrotic or scar tissue that resulted in bladder neck or intraprostatic stenosis) was 23%, 19%, and 23% in Cohorts 1, 2, and 3, respectively. Recurrent urinary tract infection occurred in 2.5%, 1.9%, 3.1% of the sample. Although comprehensive data on erectile function with validated questionnaires was not available, the post-HIFU clinical potency rate in previously potent patients was about 55%; of these patients, roughly two-thirds were taking PDE-5 inhibitors.
Our publication was quickly followed by that of Crouzet et al. (2013) from Lyon, France.[2] A total of 1 002 patients were included; 63% of which had moderate- or high-risk disease characteristics. Sixty percent of patients received one HIFU session, 38% received 2 sessions, and 2% received 3 sessions. The 10-year overall survival rate and prostate cancer-specific survival rates were 80% and 97%, respectively. Prostate cancer specific survival rates were 99% for low-risk (D’Amico) patients, 98% for intermediate-risk patients, and 92% for high-risk patients. The 10-year prostate cancer metastasis–free survival rate was 94% for the entire population and, stratified, was 99%, 95%, and 86% for low-, intermediate-, and high-risk patients, respectively. Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) scores between 12 and 24 months after HIFU. All adverse effects, such as bladder outlet obstruction (BOO) (obstruction of the outflow of urine from necrotic debris or urethral stricture), were prospectively recorded. Severe incontinence (Grade II or III) and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively, for patients treated with the prototype device to those treated with the Ablatherm Integrated Imaging. Potency was evaluated in 187 patients treated after 2005 with the latest generation of device. The median IIEF-5 score decreased from 17 (range: 5–25) to 5 (range: 1–22) (p < 0.001). Potency was preserved (IIEF ≥ 17) without pharmaceutical aid in the 42.3% of patients with a baseline IIEF score ≥ 17 (< 70 years: 55.6%; ≥ 70 years: 25.6%; p < 0.001). A return to intercourse rate was not reported but would likely be significantly higher based on the observations of Ganzer et al (2013).[1]
|
|
Risk Group |
n |
10-Year |
10-Year |
|
Ganzer et al. |
Low |
229 |
100% |
99.6% |
|
Intermediate |
211 |
96.2% |
94.3% |
|
|
Thueroff et al. |
All localized |
704 |
99% |
95% |
|
Crouzet et al. |
Low |
357 |
99% |
99% |
|
Intermediate |
452 |
98% |
95% |
|
|
High |
174 |
92% |
86% |
In our manuscript, we concluded that the “the presented data of 10 year outcomes may warrant the possible closing of the investigational phase of HIFU.” This comment was based on our stand-alone outcomes. The publications of Ganzer and Crouzet further substantiate the durability of HIFU’s oncologic control as well as demonstrate its reproducibility. It is our opinion that the investigational phase of HIFU is now definitively closed and the procedure can be considered a standard of care for localized prostate cancer.
References:
- Ganzer R, Fritsche HM, Brandtner A, Bründl J, Koch D, Wieland WF, Blana A. 14-Year oncologic and functional Outcome of High-Intensity Focused Ultrasound (HIFU) in localized prostate cancer. British Journal of Urology, In Press 2013.
- Crouzet S, et al. Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients. Eur Urol. 2013 Apr 30. (Epub ahead of print)
Written by:
Christian G. Chaussy, MD, HonFRCSEd as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Professor of Urology University of Regensburg, Germany
Clinical Professor of Urology Keck School of Medicine, University of Southern Calif., Los Angeles, CA USA
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