PSA response to antiandrogen withdrawal: a systematic review and meta-analysis

Background: Antiandrogen withdrawal (AAW) response is the paradoxical decrease in prostate-specific antigen (PSA) following the withdrawal of antiandrogen in patients with advanced prostate cancer. Currently, the reported literature on the proportion of patients exhibiting AAW response and the differences in PSA response between the types of antiandrogens is unclear. Methods: This review aimed to explore the PSA response to AAW and to identify if the response depends on the type of antiandrogens. A literature search was performed using databases PubMed, Cochrane and EMBASE with a cut-off date of 23rd of November 2020. Studies reporting on outcomes of AAW and prostate cancer were included. Studies were screened by two reviewers and relevant data extracted. Meta-analysis of outcomes was reported using random-effects and fixed-effects model. A subgroup analysis was performed for type of antiandrogen. Results: From 450 studies, 23 were included with a total of 1474 patients with advanced prostate cancer were available for further analysis. Overall, 395 (26%) patients had any reduction in PSA levels (95% CI: 20–32%) and 183 (11%) patients had a ≥50% reduction in PSA levels (95% CI: 6–16%). Among the 1212 patients on first-generation antiandrogens, 30% (95% CI: 23–38%) had any PSA decline with 15% patients having a ≥50% PSA decline (95% CI: 8–22%). In contrast, among the 108 patients on second-generation antiandrogens, 7% (95% CI: 0–13%) had any PSA decline and only 1% (95% CI: 0–5%) had a ≥50% PSA decline. Also, among the 154 patients on androgen synthesis inhibitors, 26% (95% CI: 19–33%) had any PSA decline and only 4% (95% CI: 0–13%) had a ≥50% PSA decline. Conclusions: One-fourth of patients treated with AAW show a PSA response. However, PSA response to AAW is uncommon with second-generation antiandrogens and androgen synthesis inhibitors. Further research is required to understand the differences in response between the types of antiandrogen. Refereed/Peer-reviewed