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

Abstract

Background Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized 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 conventionally 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 (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. 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 castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), 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 univariate 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 postoperative 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 radiotherapy. 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.

Radioresistance in rhabdomyosarcomas: Much more than a question of dose

“…As previously discussed, the use of higher dose per fraction has been also proposed for RMS as a consequence of the low a/b ratio (2.8 Gy) shown for this cancer type (79). However, the use of HFRT for the treatment of RMS did not lead to any improvement in efficacy (58-70), as already described for other cancer types (80)(81)(82)(83)(84). Despite being a milestone in the multimodal treatment of pediatric RMS, RT is still significantly associated with local failure in most cases of tumor relapse, and the RMS response to radiation appears to go far beyond the simple dose problem.…”

Clinicopathological and oncological significance of persistent prostate-specific antigen after radical prostatectomy: A systematic review and meta-analysis

“…From the view of the salvage radiation aspect, Murgic et al. [ 56 ] further explored that for those patients with persistent postoperative PSA, a standard fractionation RT regimen was associated with higher biochemical control compared to a commonly used hypofractionated regimen, which may be due to the higher biological dose. Additionally, they also found that the first post-prostatectomy PSA level, rather than the pre-RT PSA level, is an important prognostic factor for the success of SRT.…”

Moderately hypofractionated salvage radiotherapy in patients with biochemical recurrence of prostate cancer after prostatectomy: long-term results and comparative analysis of two schedules

“…The superiority of a normofractionated regimen (66 Gy in 33 fractions) over a hypofractionated scheme (52.5 Gy in 20 fractions) in the biochemical control of disease is reported by Murgic et al [44] According to the Authors the superiority of the normofractionated regimen is the result of the lower biological dose of the hypofractionated schedule compared to the normofractionated. Other major limitations reported by the Authors are the baseline imbalance in ADT use, ADT duration, and ISUP grade group distribution between the two radiotherapy cohorts.…”