The impact of prostate‐specific antigen persistence after radical prostatectomy on the efficacy of salvage radiotherapy in patients with primary N0 prostate cancer

Abstract

Objective To test whether salvage radiotherapy (SRT) in patients with lymph node negative (N0) prostate cancer is equally effective with persistent prostate‐specific antigen (PSA) and PSA rising from the undetectable range (<0.1 ng/mL) after radical prostatectomy (RP). Patients and methods We assessed post‐SRT PSA progression‐free survival (PFS) in 555 patients with prostate cancer. The entire cohort was compared with a risk‐adjusted subgroup of 112 patient pairs with matching pre‐RP PSA level (±10 ng/mL), Gleason score (≤6 vs 7 vs ≥8), and pre‐SRT PSA level (±0.5 ng/mL). Results The median follow‐up was 6.1 years. After RP, PSA was undetectable in 422 and persistent in 133 patients. PSA persistence and a pre‐SRT PSA level of ≥0.5 ng/mL reduced Kaplan–Meier rates of PFS significantly. In multivariate analysis of the entire cohort and after risk adjustment, the pre‐SRT PSA level but not post‐RP PSA persistence was a significant parameter. In the matched cohort's subgroup with early SRT at a PSA level of <0.5 ng/mL, a trend towards a worse outcome with post‐RP PSA persistence was observed. Delayed SRT with a PSA level ≥0.5 ng/mL led to a PFS of <30%, irrespective of the post‐RP PSA level. Conclusion In patients with N0 prostate cancer with post‐RP PSA persistence, early SRT at a PSA level <0.5 ng/mL seems to be less effective than in recurrent patients with post‐RP undetectable PSA. They might benefit from intensified therapy, but larger case numbers are required to substantiate this conclusion. In patients with a PSA level ≥0.5 ng/mL and higher‐risk features associated with post‐RP PSA persistence, SRT alone is unlikely to provide long‐term freedom from further progression.

Prognostic risk classification for biochemical relapse-free survival in patients with oligorecurrent prostate cancer after [68Ga]PSMA-PET-guided metastasis-directed therapy

“…We evaluated initial tumor stage [10] (T2c ≤ vs. ≥ T3a), initial nodal status [11] (N0 vs. N1), initial Gleason score [10,11] (7a ≤ vs. ≥ 7b), and initial resection status [11] (R0 vs. R1). Further, we evaluated the risk factors PSA persistence > 0.1 ng/mL after RP [12], PSA level at PMSA-PET imaging/recurrence [10,11], age at relapse as well as the PSMA-PET-related factors local recurrence (no vs. yes), pelvic lymph node lesions (no vs. yes), distant metastases (no vs. yes), and the number of lesions at PSMA-PET imaging. We used receiver operating characteristic (ROC) analysis to determine cutoff values for non-dichotomous variables.…”

Management of Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy: A Systematic Review of the Literature

“…In 14 retrospective studies comparing the oncologic outcomes between patients having or not having an undetectable PSA value after RP, PSA persistence was significantly correlated with poorer survival rates, according to the endpoint used (BCRFS, MFS, CSS, or OS). PSA persistence was not an independent predictive factor for BCRFS in only two studies in which all patients were treated by sRT [12,15]. Gandaglia et al [23] suggested that the impact of PSA persistence on outcomes might be influenced by the overall risk of CSM.…”

“…In comparative studies and RCTs, the proportion of patients with detectable versus those achieving an undetectable value ranged from 3.1% to 54.2% according to the selection criteria. Five studies included only patients receiving sRT [1,12,15,17,19,24]. Patients having positive lymph nodes at final pathology (pN1 disease) were excluded from analysis in six retrospective studies and five RCTs [1,12,17,19,21,24].…”

“…BCR was mainly defined as any confirmed PSA value above 0.2 ng/ml after RP [1,4,20,24]. In case of sRT, BCR was defined as any PSA rise after sRT or PSA 0.2 ng/ml above the post-sRT PSA nadir [12,17,19]. It corresponded to 5-yr BCRFS rates varying from 21.5% to 67.0% in retrospective studies when all treatment options were considered (observation, and immediate or salvage treatments).…”

PSA persistence after radical prostatectomy needs more than standard therapeutic options to improve outcomes

“…In their retrospective study, Bartkowiak et al. report the therapeutic outcomes of salvage radiation therapy (sRT) after radical prostatectomy (RP) for lymph‐node‐negative prostate cancer in 422 and 133 patients with biochemical relapse or persistently detectable PSA, respectively. In the total cohort, patients with persistent PSA serum levels ≥0.1 ng/mL postoperatively had significantly shorter progression‐free survival as compared to patients with undetectable PSA levels ( P < 0.001).…”