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

Context The prognosis and optimal management of pN0/pN1 patients with persistently elevated prostate-specific antigen (PSA) 6–8 wk after radical prostatectomy (RP) remain unclear. Objective To perform a systematic review of oncologic outcomes and effectiveness of salvage therapies in men with a detectable PSA level after RP. Evidence acquisition A systematic review was performed in May 2020. A total of 2374 articles were screened, and 25 studies including 5217 men were selected and included in the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Evidence synthesis PSA persistence was most commonly defined as PSA >0.1 ng/ml. PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes than in men with undetectable PSA levels. The 5-yr recurrence-free survival rates varied from 21.5% to 67.0%. The ≥10-yr cancer-specific survival was 75–88%. Salvage radiotherapy ± androgen deprivation therapy was associated with improved survival outcomes. Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment. The usefulness of molecular imaging in this setting remains underevaluated. Main limitations of this systematic review are the retrospective design of the included studies and the lack of randomized controlled trials (RCTs) focusing on this specific population. Conclusions PSA persistence after RP is strongly correlated with poor oncologic outcomes. Our review suggests a benefit from immediate radiotherapy; however, current evidence is still low. Indication of subsequent therapies should be based on individual discussions, taking into account all the prognostic factors and the efficacy/toxicity imbalance of proposed treatment. Results from ongoing RCTs are awaited to state on the role of more intensified systemic therapy in this population. Patient summary Patients with a detectable prostate-specific antigen level after surgery are at high risk of subsequent progression. Immediate radiotherapy might improve survival outcomes. Further research into the role of molecular imaging and genomic classifier is needed in this patient population.