Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial

Kneebone, Andrew; Fraser-Browne, Carol; Duchesne, Gillian; Fisher, Richard; Frydenberg, Mark; Herschtal, Alan; Williams, Scott; Brown, Chris; Delprado, Warick; Haworth, Annette; Joseph, David; Martin, Jarad; Matthews, John; Millar, Jeremy; Sidhom, Mark; Spry, Nigel; Tang, Colin; Turner, Sandra; Wiltshire, K.; Woo, Henry H.; Davis, Ian D.; Lim, Tee; Pearse, Maria

doi:10.1016/s1470-2045(20)30456-3

Cited by 247 publications

(211 citation statements)

References 30 publications

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“…For most patients with adverse pathologic features on RP, results of the RAVES, RADICALS, and GETUG AFU-17 randomized trials have demonstrated that adjuvant RT can now be safely omitted in favor of observation and early SRT [15][16][17]. In addition to these prospective trial data, retrospective series have suggested that early SRT is associated with clinical outcomes superior to those of delayed SRT [3,5].…”

Section: Discussionmentioning

confidence: 99%

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

Campbell

Tom

Agrawal

et al. 2022

European Urology Oncology

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Background: Salvage radiotherapy (SRT) is an established treatment for men with biochemical recurrence following radical prostatectomy (RP). There are several risk factors associated with adverse outcomes; however, the value of postoperative prostate-specific antigen (PSA) kinetics is less clear in the ultrasensitive PSA era. Objective: To characterize the impact of PSA kinetics on outcomes following SRT and generate nomograms to aid in identifying patients with an increased risk of adverse clinical outcomes. Design, setting, and participants: A multi-institutional analysis was conducted of 1005 patients with prostate cancer treated with SRT after RP, with a median followup of 5 years. Outcome measurements and statistical analysis: Variables examined include immediate postoperative PSA, postoperative PSA doubling time (DT), and pre-SRT PSA, in addition to previously identified predictive factors. Multivariable survival analyses were completed using Fine-Gray competing risk regression. Rates of biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were estimated by the cumulative incidence method. Nomograms were generated from multivariable competing risk regression with bootstrap cross-validation. Results and limitations: Factors associated with BF after SRT include PSA DT <6 mo, initial postoperative PSA 0.2 ng/ml, higher pre-SRT PSA, lack of androgen deprivation therapy, a higher Gleason score (GS), negative margins, seminal vesicle invasion, lack of pelvic nodal radiation, radiation total dose <66 Gy, a longer RP to SRT interval, and older age (p < 0.05 for each). Factors associated with DM include PSA DT <6 mo,

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Section: Discussionmentioning

confidence: 99%

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

Campbell

Tom

Agrawal

et al. 2022

European Urology Oncology

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“…RADICALS, RAVES, GETUG-AFU17 trial). In postprostatectomy radiotherapy practice, these three landmark trials will define the care of patients after prostatectomy; so far they swung pendulum towards early radiotherapy salvage, however it is important to know that patients with multiple high-risk features were not considered eligible for those trials [ 21 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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

Murgić¹,

Jakšić²,

Prpić

et al. 2021

Radiat Oncol

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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.

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“…Between 20% and 40% of men who undergo radical prostatectomy (RP) for prostate cancer will develop a biochemical recurrence (BCR), typically defined as a post-RP prostate-specific antigen (PSA) value of !0.2 ng/mL [1,2]. There is now clear evidence from large randomized trials that early salvage radiotherapy (SRT) provides the same oncological benefit as adjuvant radiotherapy (RT), but with a much better toxicity profile, and with avoidance of RT in about half of patients with high-risk features on pathological assessment after RP [3,4]. Accordingly, the number of patients being considered for SRT is expected [5] to increase.…”

Section: Introductionmentioning

confidence: 99%

Use and Impact of Positron Emission Tomography/Computed Tomography Prior to Salvage Radiation Therapy in Men with Biochemical Recurrence After Radical Prostatectomy: A Scoping Review

Valle

Shabsovich

Meerleer

et al. 2021

European Urology Oncology

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Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial

Cited by 247 publications

References 30 publications

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

Integrating Prostate-specific Antigen Kinetics into Contemporary Predictive Nomograms of Salvage Radiotherapy After Radical Prostatectomy

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

Use and Impact of Positron Emission Tomography/Computed Tomography Prior to Salvage Radiation Therapy in Men with Biochemical Recurrence After Radical Prostatectomy: A Scoping Review

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