title: PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.
abstract: Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting.
  
  
  
  An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases.
  
  
  
  Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%).
  
  
  
  In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, Whittington Hospital NHS Trust, London, UK.
authors.forename: T T
authors.identifier: 0000-0003-1642-1208
authors.initials: TT
authors.lastname: Shah
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kanthabalan
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: McCartan
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Fatola
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van der Voort van Zyp
authors.affiliation: Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Vulpen
authors.affiliation: Department of Histopathology, UCLH NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Moore
authors.affiliation: Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Arya
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.|NIHR UCLH/UCL Comprehensive Biomedical Research Centre, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Emberton
authors.affiliation: Division of Surgery and Interventional Science, UCL, London, UK.|Department of Urology, UCLH NHS Foundation Trust, London, UK.
authors.forename: H U
authors.initials: HU
authors.lastname: Ahmed
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D018450:Disease Progression; D005500:Follow-Up Studies; D057086:High-Intensity Focused Ultrasound Ablation; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D060787:Neoplasm Grading; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen