PURPOSE: Recent advancements in the management of biochemical recurrence (BCR) following
local treatment for prostate cancer (PCa), including the use of androgen receptor
signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options.
We aimed to compare salvage therapies in patients with BCR after definitive local
treatment for clinically non-metastatic PCa with curative intent. METHODS: In October
2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized
controlled trials (RCTs) and prospective studies reporting data on the efficacy of
salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation
therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary
endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS:
We included 19 studies (n = 9117); six trials analyzed RT-based strategies following
RP, ten trials analyzed hormone-based strategies following RP +/- RT or RT alone,
and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone
therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p <
0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies,
the addition of elective nodal RT and androgen deprivation therapy (ADT) was found
to be the most effective in terms of MFS. On the other hand, among hormone-based strategies,
enzalutamide + ADT showed the greatest benefit for both MFS and OS. CONCLUSIONS: The
combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred
treatment for eligible patients with post-RP BCR based on our analysis. In remaining
patients, or in case of post-RT recurrence, especially for those with high-risk BCR,
the combination of ADT and ARSI should be considered.
