Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy

Abstract

The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and < 66 Gy groups (n = 66) were compared using the Log-rank test, followed by univariate and multivariate analyses and a subgroup analysis. After a median follow-up of 73 months, 6-year biochemical relapse-free survival, cRFS, cancer-specific survival, and overall survival rates were 58, 92, 98, and 94%, respectively. Six-year cRFS rates in the ≥ 66 Gy and < 66 Gy groups were 94 and 87%, respectively (p = 0.022). The multivariate analysis revealed that Gleason score ≥ 8, seminal vesicle involvement, PSA at BCR after RP ≥ 0.5 ng/ml, and a dose < 66 Gy correlated with clinical relapse (p = 0.015, 0.012, 0.024, and 0.0018, respectively). The subgroup analysis showed the consistent benefit of a dose ≥ 66 Gy in patients across most subgroups. Doses ≥ 66 Gy were found to significantly, albeit borderline, increase the risk of late grade ≥ 2 GU toxicity compared to doses < 66 Gy (14% vs. 3.2%, p = 0.055). This large multi-institutional retrospective study demonstrated that a higher SRT dose (≥ 66 Gy) resulted in superior cRFS.

Figure 1

Flowchart of the study cohort. SRT salvage radiotherapy, BCR biochemical recurrence, RP radical prostatectomy, PSA prostate-specific antigen, ADT androgen deprivation therapy, EQD2 equivalent dose in 2-Gy fractions.

Figure 2

Kaplan–Meier curves of biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS), and overall survival (OS) for all patients (n = 292) receiving salvage radiotherapy for biochemical recurrence after radical prostatectomy.

Figure 3

Kaplan–Meier curves of clinical relapse-free survival (cRFS) for patients receiving total doses of ≥ 66 Gy (n = 226) vs. < 66 Gy (n = 66) in an equivalent dose in 2-Gy fractions (EQD2).

Figure 4

Effects of radiation doses by clinical and pathological risk factors. EQD2 equivalent dose in 2-Gy fractions, HR hazard ratio, 95% CI 95% confidence interval, SVI seminal vesicle involvement, PSA prostate-specific antigen, BCR biochemical recurrence, RP radical prostatectomy, ECE extracapsular extension, SRT salvage radiotherapy.

Figure 5

Cumulative incidence curves of late grade 2 or higher (a) genitourinary and (b) gastrointestinal toxicities for patients receiving total doses of ≥ 66 Gy (n = 226) vs. < 66 Gy (n = 66) in an equivalent dose in 2-Gy fractions (EQD2).