PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure

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.Prostate Cancer and Prostatic Diseases advance online publication, 19 July 2016; doi:10.1038/pcan.2016.23.

Prostate cancer and prostatic diseases. 2016 Jul 19 [Epub ahead of print]

T T Shah, M Peters, A Kanthabalan, N McCartan, Y Fatola, J van der Voort van Zyp, M van Vulpen, A Freeman, C M Moore, M Arya, M Emberton, H U Ahmed

Division of Surgery and Interventional Science, UCL, London, UK., Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands., Division of Surgery and Interventional Science, UCL, London, UK., Division of Surgery and Interventional Science, UCL, London, UK., Division of Surgery and Interventional Science, UCL, London, UK., Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands., Department of Radiation Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands., Department of Histopathology, UCLH NHS Foundation Trust, London, UK., Division of Surgery and Interventional Science, UCL, London, UK., Department of Urology, UCLH NHS Foundation Trust, London, UK., Division of Surgery and Interventional Science, UCL, London, UK., Division of Surgery and Interventional Science, UCL, London, UK.