Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature

Abstract

Objective: To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a).

Patients and methods: PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery.

Results: Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%).

Conclusions: Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.

Keywords: outcome; prostate cancer; prostate-specific antigen; prostatectomy; risk.

Fig. 1

Cancer-specific outcomes stratified by risk category. (A) Biochemical recurrence free survival. Proportion of patients free from biochemical recurrence at 10 years was 77% and 61%, for Pii and Pih patients respectively. In comparison, low, intermediate, and high risk patients had 10 year BFS of 91%, 68%, and 43%, respectively. P < 0.0001 for all comparisons. (B) Metastasis free survival. Proportion of patients free from metastasis at 10 years was 97% and 90%, for Pii and Pih patients respectively. In comparison, low, intermediate, and high risk patients had 10 year MFS of 99%, 92%, and 75%, respectively. P < 0.0001 for all comparisons. (C) Cancer-specific survival. Proportion of patients free from cancer-specific death at 10 years was 99% and 92%, for Pii and Pih patients respectively. In comparison, low, intermediate, and high risk patients had 10 year CSS of 99.5%, 96%, and 85%, respectively. P < 0.0001 for all comparisons.

Fig. 2

Kaplan Meier curves comparing all PSA-incongruent men (both Pii and Pih risk) having PSA density <0.15 ng/mL/g to D’Amico low risk men. (A) Biochemical recurrence free survival, P = 0.9622. (B) Metastasis free survival, P = 0.7934. (C) Cancer-specific survival, P = 0.3781.

Fig. 3

Percentage of tumors with an anterior component found at RP, stratified by random samples of 100 patients per risk group.