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

Abstract

BackgroundTreatment options for radio-recurrent prostate cancer are either androgen deprivation therapy or salvage prostatectomy. Whole-gland HIFU might have a role in this setting.MethodsAn 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 localized disease following prior external beam radiotherapy (2005-2012).No upper threshold was applied for risk category, Prostate Specific Antigen (PSA), or Gleason grade either at presentation or at time of failure.Progression was defined as a composite with either biochemical failure (Phoenix criteria [PSA>nadir+2ng/mL]), start of systemic therapies or metastases.ResultsMedian age (IQR), pre-treatment PSA (IQR), and Gleason score (range), were 68years (64-72), 5.9ng/mL (2.2-11.3), and 7 (6-9), respectively. Median follow-up was 64months (49-84).24/50 (48%) avoided androgen deprivation therapies. 28/50 (56%) achieved a PSA-nadir <0.5ng/ml. 15/50 (30%) had a nadir ≥0.5ng/ml. 7/50 (14%) did not nadir (PSA non-responders).Actuarial 1, 3 and 5-year PFS was 72%, 40% and 31%, respectively. Actuarial 1, 3, and 5-year OS was 100%, 94% and 87%, respectively.When comparing patients with PSA nadir <0.5ng/ml, nadir ≥0.5 and non-responders a statistically significant difference in PFS was seen (p<0.0001). 3-year PFS in each group was 57%, 20% and 0%, respectively. 5-year overall survival was 96%, 100% and 38%, respectively.Early in the learning curve, between 2005-2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measures questionnaires showed incontinence (any pad-use) as 8/26 (31%).ConclusionsIn 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 whilst retaining disease control rates is required.

Functional Outcomes after Local Salvage Therapies for Radiation-Recurrent Prostate Cancer Patients: A Systematic Review

“…A total of 35 studies published between 2005 and 2020 met our inclusion criteria: 14 prospective [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and 21 retrospective studies. Three studies evaluated surgery as salvage therapy [ 26 , 27 , 40 ], while one study [ 41 ] included surgery and HIFU as salvage modalities and provided separate analyses for each.…”

“…Primary treatment included a variation of EBRT alone, BT alone, a combination of both or proton beam therapy. EBRT was the sole primary modality in 13 studies [ 27 , 28 , 30 , 31 , 32 , 34 , 36 , 39 , 42 , 43 , 44 , 45 , 46 ], while BT was the only primary modality in one report [ 35 ]. In three studies, the primary treatment modality was not specified [ 37 , 47 , 48 ].…”

“…Across all studies, ADT was initiated as adjuvant therapy in four studies [ 28 , 42 , 54 , 56 ], neoadjuvant therapy in seven studies [ 30 , 33 , 36 , 37 , 41 , 44 , 50 ], and both adjuvant and neoadjuvant in two studies [ 29 , 40 ]. Nineteen studies reported on ADT with no further details [ 26 , 31 , 32 , 34 , 35 , 39 , 43 , 45 , 46 , 48 , 49 , 51 , 52 , 53 , 55 , 57 , 58 , 59 ], and three studies did not report on the use of ADT [ 27 , 38 , 47 ]. Table 1 summarizes the characteristics of the included studies.…”

“…In studies reporting on non-surgical salvage interventions, continence was measured using scores such as the Ingelman-Sundberg score and the University of California Los Angeles (UCLA) urinary continence domain in addition to the number of pads. In the 13 studies that evaluated salvage HIFU, the reported UI rates ranged from 7.5% to 60.7% [ 31 , 32 , 33 , 34 , 35 , 36 , 41 , 42 , 44 , 45 , 46 , 56 , 57 ]. The rate of severe UI among these studies was less than 18% in eight studies, while Hostiou et al and Jones et al reported severe UI rates of 42% and 29%, respectively [ 31 , 35 ].…”

“…The rate of severe UI among these studies was less than 18% in eight studies, while Hostiou et al and Jones et al reported severe UI rates of 42% and 29%, respectively [ 31 , 35 ]. Three studies did not provide detailed information [ 32 , 44 , 57 ].…”