Outcomes in patients with Gleason score 8-10 prostate cancer: relation to preoperative PSA level

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High-grade prostate cancers are associated with poor disease-specific outcomes. A proportion of these tumours produce little PSA. This study demonstrates that among Gleason 8-10 prostate cancers, some of the worst survival outcomes are associated with the lowest PSA levels.

Objective: • To assess outcomes of patients with Gleason score 8-10 prostate cancer (CaP) with a low (≤ 2.5 ng/mL) vs higher preoperative serum PSA levels.

Patients and methods: • From 1983 to 2003, 5544 patients underwent open radical prostatectomy, of whom 354 had a Gleason 8-10 tumour in the prostatectomy specimen. • Patients were stratified according to preoperative PSA level into four strata: ≤ 2.5 ng/mL (n= 31), 2.6-4 ng/mL (n= 31), 4.1-10 ng/mL (n= 174), and >10 ng/mL (n= 118). • We compared biochemical progression-free survival (PFS), metastasis-free survival (MFS), and cancer-specific survival (CSS) as a function of preoperative PSA level.

Results: • Patients with PSA level ≤ 2.5 ng/mL were more likely to have seminal vesicle invasion (P= 0.003). • On Kaplan-Meier survival analysis, patients with a PSA level ≤ 2.5 ng/mL had proportionately worse outcomes than their counterparts with higher PSA levels. • The 7-year PFS in the PSA ≤ 2.5 ng/mL stratum was lower than those of the PSA 2.6-4 ng/mL and 4-10 ng/mL strata (36% vs 50 and 42%, respectively); however, the lowest 7-year PFS was found in those with a PSA level >10 ng/mL (32%, P= 0.02). • Gleason score 8-10 tumours with a PSA level ≤ 2.5 ng/mL also tended to have the lowest 7-year MFS (75, 93, 89 and 92% for PSA level ≤ 2.5, 2.6-4, 4.1-10 and >10 ng/mL, respectively, P= 0.2) and CSS (81, 100, 94 and 90% for PSA level ≤ 2.5, 2.6-4, 4.1-10 and >10 ng/mL, respectively, P= 0.3), although these differences were not statistically significant. • In the subset with palpable disease, Gleason grade 8-10 disease with PSA level ≤ 2.5 ng/mL also was associated with a worse prognosis.

Conclusions: • In patients with Gleason grade 8-10 disease, a proportion of these tumours are so poorly differentiated that they produce relatively little PSA. • Patients with high-grade, low-PSA tumours had less favourable outcomes than many of those with higher PSA levels.