Prostate-specific antigen doubling time as a progression criterion in an active surveillance programme for patients with localized prostate cancer.

Abstract

To elucidate the role of prostate-specific antigen (PSA) doubling time (PSAdt) as a progression criterion in patients with low-risk prostate cancer managed by active surveillance (AS). To assess the correlation between PSAdt during AS and final histopathology after radical prostatectomy (RP) in patients meeting predefined progression criteria. A total of 258 consecutive patients on an AS programme were included in the study. The PSAdt was calculated in patients with two or more PSA values, and 95% confidence intervals (CIs) were calculated in patients with four or more PSA values. Progression risk groups were defined as follows: high-risk: PSAdt <3 years, rebiopsy Gleason score (GS) ≥4 + 3, more than three positive biopsy cores, and/or bilateral tumour or cT ≥2c disease; intermediate-risk: PSAdt 3-5 years, GS = 3 + 4 or cT2b disease; and low-risk: PSAdt >5 years, without histopathological or clinical progression. Definitive treatment was recommended for patients in the high-risk group and treatment options were discussed with those in the intermediate-risk group. A total of 2291 PSA values obtained during AS were available, of which 2071 were considered valid in the 258 patients. PSAdt values with 95% CIs were calculated in 221 patients based on a median of 8 PSA values. The 95% CIs for PSAdt overlapped considerably and in up to 91% of the patients, the 95% CIs overlapped among the risk group definitions. A total of 26% (68/258 patients) underwent RP after meeting the progression criteria. There was no association between preoperative PSAdt and final histopathology (P = 0.87). The uncertainty of calculated PSAdt during AS leads to a significant risk of patients being misclassified in terms of risk of progression, which limits the use of PSAdt in the management of patients on AS.