Undetectable PSA predicts outcome after salvage radiotherapy for biochemical recurrence following radical prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiotherapy (SRT) is a curative treatment option in patients with biochemical recurrence after radical prostatectomy (RP). Undetectable prostate-specific antigen (PSA) < 0.1 ng/mL following SRT predicts biochemical progression-free survival (BPFS). The aim of this large retrospective study was to evaluate whether this effect persists in an extended follow-up of >5 years. MATERIALS AND METHODS: A total of 678 patients treated with SRT for biochemical recurrence after RP were included. Exclusion criteria were lymph node or distant metastases, pre-SRT PSA > 3 ng/mL, and receipt of androgen deprivation therapy (ADT) between RP and SRT. All patients received a median dose of 70.2 (range 59.4-72.0) Gy to the prostatic fossa. The log-rank test (Kaplan-Meier) and Cox regression analysis were used to evaluate the impact of disease- and treatment-related parameters on BPFS, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Median follow-up after SRT was 5.6 (range 0.1-14.5) years. The 5-year BPFS was 77.8 % in patients with a PSA nadir < 0.1 ng/mL (undetectable) and 16.3 % in the remaining cohort (p < 0.001). Five-year MFS was 95.3 % with undetectable PSA versus 84.0 % with detectable PSA (p < 0.001), and 5-year OS values were 97.5 % and 92.7 % with undetectable versus detectable PSA, respectively (p = 0.04). In multivariate analysis, undetectable PSA was the strongest predictor of BPFS (HR = 0.122; 95 %CI: 0.080-0.187; p < 0.001) and MFS (HR = 0.262; 95 %CI: 0.136-0.594; p < 0.001), but was not significant for OS (HR = 0.615; 95 %CI: 0.298-1.269; p = 0.189). CONCLUSION: PSA < 0.1 ng/mL following SRT without ADT is a significant predictor of BPFS and MFS. The results suggest that it might be feasible to withhold ADT in selected patients if they have undetectable PSA after SRT. Prospective studies are warranted to confirm these findings.

European association of urology risk stratification predicts outcome in patients receiving PSMA-PET-planned salvage radiotherapy for biochemical recurrence following radical prostatectomy.

PURPOSE: The European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET. METHODS: For this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients. RESULTS: The median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis-free survival (MFS) was 94.4 % in low-risk versus 87.6 % in high-risk patients (p = 0.005). The 3-year overall survival (OS) was 99.0 % in low-risk versus 99.6 % in high-risk patients (p = 0.925). In multivariate analysis, EAU risk group remained a statistically significant predictor of BPFS (p = 0.003, HR 2.022, 95 % CI 1.262-3.239) and MFS (p = 0.013, HR 2.986, 95 % CI 1.262-7.058). CONCLUSION: Our data support the EAU risk group definition. EAU risk grouping for BCR reliably predicted outcome in patients staged lymph node-negative after RP and with PSMA-PET before SRT. To our knowledge, this is the first study validating the EAU risk grouping in patients treated with PSMA-PET-planned SRT.

Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study.

BACKGROUND/PURPOSE: The present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). MATERIALS AND METHODS: This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. RESULTS: The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant. CONCLUSION: To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.

Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis.

Previous randomized trials have not provided conclusive evidence about dose escalations and associated toxicities for salvage radiotherapy (SRT) in prostate cancer. Here, we retrospectively analyzed whether dose escalations influenced progression-free survival in 554 patients that received salvage radiotherapy for relapses or persistently elevated prostate cancer antigen (PSA) after a radical prostatectomy. Patients received SRT between 1997 and 2017 at two University Hospitals in Germany. We compared patient groups that received radiation doses <7000 cGy (n = 225) or ≥7000 cGy (n = 329) to analyze the influence of radiation dose on progression-free survival. In a second matched-pair analysis of 216 pairs, we evaluated prognostic factors (pT2 vs. pT3−4, Gleason score [GS] ≤ 7 vs. GS ≥ 8, R0 vs. R1, and pre-SRT PSA <0.5 vs. ≥0.5 ng/mL). After a median follow-up of 6.8 (4.2−9.2) years, we found that escalated doses significantly improved progression-free survival (p = 0.0042). A multivariate analysis indicated that an escalated dose, lower tumor stages (pT2 vs. pT3/4), and lower GSs (≤7 vs. 8−10) were associated with improved progression-free survival. There was no significant effect on overall survival. Our data suggested that escalating the radiation dose to ≥7000 cGy for SRT after a prostatectomy significantly improved progression-free survival. Longer follow-ups are needed for a comprehensive recommendation.