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

Abstract

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.

Prostate carcinoma: correlation of histopathology with serum prostate specific antigen

“…In a study of 354 patients with carcinoma prostate (Gleason score 8-10) by McGuire BB et al, 17.5% had PSA level<4ng/ml [17] . In a similar study by Thompson IM et al, 15.2% had PSA <4ng/ml, out of which 14.9% had a Gleason score of 7 or higher [6] .…”

“…This could result in these tumours being diagnosed at a later stage than tumours producing more PSA. Also, patients with high grade, low PSA tumours have poorer prognosis than those of higher PSA levels [17] . The mean value of S.PSA in Grade 1 Adenocarcinoma was 8ng/ml, in Grade 2 was 42.5ng/ml, in Grade 3 was 44.1ng/ml and in Grade 4 was 61.8ng/ml.…”

“…According to them, PSA production decreases with increasing histological grade [12] . The lack of correlation between Gleason score and PSA may be explained by decrease in production of antigen by higher grade lesions due to loss of expression of PSA encoding gene [10], [17] .…”

The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level <2.5ng/ml

“…Several studies have explored the relationship between pretreatment PSA level and clinical outcomes, including recurrence and death, when serum PSA levels are ''normal'' ( [10][11][12]). A few have suggested that in certain situations the association may be inverse -that higher PSA can be associated with a better outcome ( [11,12]).…”

“…A few have suggested that in certain situations the association may be inverse -that higher PSA can be associated with a better outcome ( [11,12]). This finding is consistent with the clinical observation that there is a subgroup of men with low serum PSA, yet biologically aggressive PC.…”