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Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience

Background:Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no rand-omized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for convention-ally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed.Methods:Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.Results:Sixty-nine patients who had persistent PSA (≥0.1ng/mL) after prostatectomy were identified. Median follow-up was 67months (95% CI 58–106months, range, 8–106months). Thirty- six patients (52.2%) received CFR, 66Gy in 33 fractions, 2Gy per fraction, and 33 patients (47.8%) received HFR, 52.5Gy in 20 fractions, 2.63Gy per frac-tion. Forty-seven (68%) patients received androgen deprivation therapy (ADT ). 5- year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic cas-tration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72months (95% CI ; 41–72months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2 ; 95% CI 1.0–4.6, p=0.04). On uni-variate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p=0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p=0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p=0.02). On multivariate analysis, factors significantly associated with PSA failure- free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p=0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p=0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postop- erative PSA (HR 1.07, 95% CI 1.03–1.12, p=0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26– 9.6, p=0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p=0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p=0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00– 1.08, p=0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p=0.04) remained significantly associated with metastasis-free survival on multivariate analysis.Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity.Conclusions:In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radio-therapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post- prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations

radical prostatectomy ; prostate cancer ; salvage radiotherapy ; Hypofractionation ; standard fractionation ; prostate-specific antigen persistence ; androgen deprivation therapy

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