https://doi.org/10.4081/aiua.2026.14731
Prognostic value of Ki67 and PSA-immunostaining in de novo metastatic hormone-sensitive prostate cancer
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Published: 31 March 2026
Introduction: Prostate cancer comprises biologically distinct subtypes. Ki67 reflects tumour proliferation, while prostate-specific antigen immunostaining (PSA-IHC) indicates differentiation, with low PSA-IHC suggesting dedifferentiation. The prognostic role of these markers in de novo metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear.
Aim: To evaluate the prognostic value of Ki67 and PSA-IHC, individually and combined, in de novo mHSPC, and explore their relevance across treatment modalities.
Methods: We retrospectively analysed patients diagnosed with de novo mHSPC (2015-2020) who ultimately died from prostate cancer. Clinical data included age, ISUP grade, baseline and 7-month PSA, metastatic sites, and first-line treatment. Ki67 (MIB-1) and PSA-IHC were quantified as the percentage of positive nuclei and cytoplasmic staining, respectively. The 75th percentile defined high vs low expression. Endpoints were biochemical (bPFS), radiological (rPFS), castration-resistant progression-free survival (CRPC-FS), and overall survival (OS). Exploratory analyses were performed by treatment type: androgen receptor pathway inhibitors (ARPIs) or taxanes.
Results: Sixty-seven patients were included (median age 77 years). Most had high-grade tumours (ISUP ≥3, 83.6%). High Ki67 (>P75) correlated with shorter OS (10 vs 21 months, p=0.013). PSA-IHC >P75 predicted longer bPFS (13 vs 9 months, p=0.027). Combined stratification identified distinct prognostic groups (p=0.034): PSA-IHC low/Ki67 high defined a high-risk phenotype with poor outcomes, particularly among taxane-treated patients (p=0.006).
Conclusions: Combined Ki67 and PSA-IHC assessment refines risk stratification in de novo mHSPC, identifying a high-risk PSA-IHC low/Ki67 high subgroup with markedly worse prognosis. These findings warrant prospective validation.
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CRediT authorship contribution
Ana Marta Ferreira: Acquisition of clinical data; data curation; data analysis and interpretation; drafting of the original manuscript; critical revision for important intellectual content; Roberto Jarimba: Study conception and design; data curation; data analysis and interpretation; statistical analyses; validation of results; review and editing of the manuscript; André Rego: Data curation; data analysis and interpretation; statistical analyses; preparation of tables and figures; review and editing of the manuscript; João Gama: Data curation; data analysis and interpretation; substantial contribution to manuscript writing; critical revision for important intellectual content; language editing; Rui Almeida: Data curation; data analysis and interpretation; substantial contribution to manuscript writing; critical revision for important intellectual content; language editing; Miguel Eliseu: Substantial contribution to manuscript writing; critical revision for important intellectual content; language editing; Vasco Quaresma: Substantial contribution to manuscript writing; critical revision for important intellectual content; language editing; Pedro Nunes: Study concept and design; supervision; contribution to manuscript writing and editing; overall project administration; approval of the final version; Vitor Sousa: Study concept and design; supervision; contribution to manuscript writing and editing; overall project administration; approval of the final version; Arnaldo Figueiredo: Funding, study concept and design; supervision; contribution to manuscript writing and editing; overall project administration; approval of the final version.
Supporting Agencies
Associação dos Amigos da Urologia e Transplantação RenalData Availability Statement
The datasets generated and/or analyzed during the current study are not publicly available due to ethical and legal restrictions imposed by the hospital's data protection policies, but de-identified data may be available from the corresponding author upon reasonable request and with appropriate institutional approvals.
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