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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Frederik Birkebaek
FB
Thomsen
Ib Jarle
IJ
Christensen
Klaus
K
Brasso
Martin Andreas
MA
Røder
Peter
P
Iversen
D000368:Aged; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood*; D018570:Risk Assessment; D013997:Time Factors; D057832:Watchful Waiting
D017430:Prostate-Specific Antigen
PSA doubling time; active surveillance; progression criterion; prostate cancer