AUA 2018: Salvage High-Intensity Focused Ultrasound For Locally Recurrent Prostate Cancer after Low-Dose-Rate Brachytherapy: Oncologic and Functional Outcomes

San Francisco, CA (UroToday.com) According to the EAU-ESTRO-SIOG 2018 guidelines, the biochemical disease-free survival for Gleason 6 prostate cancer at 5 years ranges from 71-93% and at 10 years from 65-85%. However, there is a lack of studies evaluating salvage therapies for locally recurrent prostate cancer after low-dose-rate (LDR) brachytherapy. The majority of cases receive androgen deprivation therapy, which is essentially palliative treatment and associated with significant adverse effects such as depression, osteopenia, fatigue, loss of libido, etc. According to Thomas Hostiou, MD there is no distinction between salvage therapy for local failure after EBRT and after LDR brachytherapy. As such, the objective of their study presented at the late-breaking session of the AUA was to evaluate oncologic and functional outcomes of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after LDR brachytherapy.
           
This was a clinical phase II study that included 50 consecutive patients between 2003 and 2015 who were previously treated with brachytherapy, had a PSA recurrence, and histologically proven local recurrence and negative metastatic evaluation (since 2012, all patients have had a choline PET scan evaluation). All patients were treated with S-HIFU. Initially, from 2003-2007 S-HIFU used post-external beam radiotherapy (EBRT) acoustic parameters. Since 2008, specific post-brachytherapy acoustic parameters (i.e. decrease of thermic intensity) were applied. Whole gland treatment was initially uniform, however, since 2009 in cases of unilateral prostate cancer identified with mpMRI and targeted biopsies, hemiablation has been performed. The primary outcome for this study was progression-free survival (PFS) defined as: (i) absence of biochemical failure (PSA < nadir + 2 ng/mL) and (ii) absence of introduction of adjuvant therapy. Secondary outcomes included: (i) overall survival, (ii) cancer-specific survival, (iii) metastasis free survival, (iv) complications, (v) continence, (vi) IPSS, (vii) IIEF-5, and (viii) health related quality of life.
           
There were 13 patients treated with post-EBRT parameters, 37 with post-brachytherapy parameters, 35 with whole gland treatments, and 15 hemiablations. The median patient age was 69 [range 63-72], median pre-treatment was PSA 5.3ng/mL [range 2.7-7.3]. Cancer location included 30 patients with unilateral disease, 20 patients with bilateral disease and 8 patients with seminal vesicle invasion. The median follow-up was 4.6 years and the post-S-HIFU median PSA was 0.3ng/ml [0.1-0.9]. Grade III complications occurred in 48% of patients. At 5 years, the PFS rate was 41%, OS rate was 93%, CSS rate was 96%, and MFS rate was 80%. There were nine patients that developed metastases, among those, only two had a choline PET scan before S-HIFU and metastases was discovered within 13 months in five patients. Post-brachytherapy compared to post-EBRT parameters reduced grade 2-3 incontinence: 34% vs 62% (p=0.015). Incontinence (regardless of rank), bladder outlet obstruction and grade ≥III complications were significantly reduced with hemiablation compared to whole gland treatment (14% vs 54%, p<0.001; 13% vs 46%, p=0.03; 13% vs 63% p=0.001, respectively).

Hostiou notes several limitations:

  • A single institution study
  • No control group
  • Small number of patients and absence of predictive factors for failure
  • Heterogeneity of patients without limit on characteristics of prostate cancer
  • Early experience with adaptions in the course of S-HIFU
  • Oncologic results need longer follow-up and are difficult for a new treatment modality
In conclusion, Hostiou highlighted several take-home messages including that (i) this is the largest series of salvage therapy for local recurrence after LDR brachytherapy, (ii) data suggests S-HIFU post-brachytherapy had more treatment-related toxicity than post-EBRT, (iii) S-HIFU post-brachytherapy had more treatment-related toxicity than post-EBRT, and (iv) using dedicated parameters and hemiablation may achieve a favorable efficacy/toxicity ratio.

Presented by: Thomas Hostiou, MD, Hospices civils de Lyon, Edouard Herriot Hospital, Department of Urology and Transplantation Surgery, Lyon, France
Co-Authors: Albert Gelet, Jean Yves Chapelon, Olivier Rouvière, Florence Mege Lechevalier, Helene Tonoli-Catez, Pascal Pommier, Lionel Badet, Sebastien Crouzet, Lyon, France

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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