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

ABSTRACT:

Background

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.

Methods

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.

Results

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%).

Conclusions

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.

SUBMITTER: Shah TT

PROVIDER: S-EPMC4983180 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and methodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 - Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.