A low prostate specific antigen predicts a worse outcome in high but not in low/intermediate-grade prostate cancer

• Published in: European journal of cancer (1990) Vol. 181; pp. 70 - 78
• Main Authors: Fankhauser, Christian D., Parry, Matthew G., Ali, Adnan, Cowling, Thomas E., Nossiter, Julie, Sujenthiran, Arun, Berry, Brendan, Morris, Melanie, Aggarwal, Ajay, Payne, Heather, van der Meulen, Jan, Clarke, Noel W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2023; Elsevier Science Ltd
• Subjects: Androgen deprivation therapy; Antigens; Brachytherapy; Cancer surgery; Confidence intervals; Health hazards; Humans; Male; Prostate cancer; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms - surgery; Radiation therapy; Radiotherapy; Regression; Retrospective Studies; Statistical analysis; Urological surgery; Prostatectomy; Brachytherapy; Androgen deprivation therapy; Radiotherapy; Prostate-specific antigen; Prostate cancer
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2022.12.017

The relationship between prostate-specific antigen (PSA) and prostate cancer (PCa) grade was traditionally thought to be linear but recent reports suggest this is not true in high-grade cancers. We aimed to compare the association between PSA and PCa-specific mortality (PCSM) in clinically localised low/intermediate and high-grade PCa. Retrospective cohort study using the National Prostate Cancer Audit database in England of men treated with external beam radiotherapy (EBRT), EBRT and brachytherapy boost (EBRT + BT), radical prostatectomy or no radical local treatment between 2014 and 2018. Multivariable competing-risk regression was used to examine the association between PSA, Gleason, and PCSM. Multivariable restricted cubic spline regression was used to explore the non-linear associations of PSA and PCSM. 102,089 men were included, of whom 71,138 had low/intermediate-grade and 22,425 had high-grade PCa. In high-grade, 4-year PCSM was higher with PSA ≤5 than PSA 5.1–10 for men treated with EBRT (hazard ratio 1.96 (95% confidence interval 1.15–3.34) or no radical local treatment (hazard ratio 1.99 (95% confidence interval 1.33–2.98). Restricted cubic spline regression showed that PSA and PCSM have a non-linear association in high-grade but a linear association in low/intermediate-grade PCa. The low-PSA/high-grade combination in M0 PCa treated with EBRT has a higher PCSM than those with high-grade and intermediate PSA levels. In high-grade disease, the PSA association was non-linear; by contrast, low/intermediate-grade had a linear relationship. This confirms a more aggressive biology in low PSA secreting high-grade PCa and a worse outcome following treatment. •Large dataset describing the prognostic value of prostate-specific antigen (PSA) in localised prostate cancer.•In high-grade prostate cancer, a low or high PSA predicts poor outcomes.•In low/intermediate-grade prostate cancer, the higher the PSA the worse the outcome.•This confirms a more aggressive biology in low PSA secreting high-grade PCa.