[−2]proPSA versus ultrasensitive PSA fluctuations over time in the first year from radical prostatectomy, in an high-risk prostate cancer population: A first report

Abstract

Background[−2]proPSA and its derivatives have an higher diagnostic accuracy than PSA in predicting prostate cancer (PCa). In alternative to PSA, ultrasensitive PSA (uPSA) and [−2]proPSA could be potentially useful in recurrent disease detection. This research focused on [−2]proPSA and uPSA fluctuations over time and their possible clinical and pathological determinants, in the first year after RP.MethodsA cohort of 106 consecutive patients, undergoing RP for high-risk prostate cancer (pT3/pT4 and/or positive margins), was enrolled. No patient received either preoperative/postoperative androgen deprivation therapy or immediate adjuvant RT, this latter for patient choice. [−2]proPSA and uPSA were measured at 1, 3, 6, 9, 12 months after RP; their trends over time were estimated by the mixed-effects linear model. The uPSA relapse was defined either as 3 rising uPSA values after nadir or 2 consecutive uPSA >0.2 ng/ml after RP.ResultsThe biochemical recurrence (BCR) rate at 1 year after RP was either 38.6 % (in case of 3 rising uPSA values) or 34.9 % (in case of PSA >0.2 ng/ml after nadir), respectively. The main risk factors for uPSA fluctuations over time were PSA at diagnosis >8 ng/ml (p = 0.014), pT (p = 0.038) and pN staging (p = 0.001). In turn, PSA at diagnosis >8 ng/ml (p = 0.012) and pN (p < 0.001) were the main determinants for [−2]proPSA trend over time. In a 39 patients subgroup, uPSA decreased from month 1 to 3, while [−2]proPSA increased in 90 % of them; subsequently, both uPSA and [−2]proPSA increased in almost all cases. The [−2]proPSA trend over time was independent from BCR status either in the whole cohort as well in the 39 men subgroup.ConclusionsBoth uPSA and [−2]proPSA had independent significant fluctuations over time. PSA at diagnosis >8 ng/ml and pathological staging significantly modified both these trends over time. Since BCR was not confirmed as determinant of [−2]proPSA fluctuations, its use as marker of early biochemical relapse may not be actually recommended, in an high-risk prostate cancer patients population.

Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2

“…We found that only PSA was able to correlate with BCR at the first (AUC 0.64; p-value 0.03) and third month (AUC 0.72; p-value 0.0004) after RP and all other markers tested such as fPSA, %fPSA, hK2, hK2/fPSA, hK2/%fPSA, [-2]proPSA and PHI were devoid of any predictive value (p-value>0.05). Similar findings were obtained by S. De Luca et al [23] who tested [-2]proPSA in a group of high-risk patients at 3-month intervals in the first year after RP. Conversely, Casale et al [24] concluded that [-2]proPSA could be of use in detecting recurrence earlier than standard PSA in a cohort of 134 patients after RP with a follow up of three years.…”

“…To our knowledge, besides one study comparing the trends of [-2]proPSA and uPSA in the first year after RP in a high-risk population [23], and a second study [24] comparing the kinetics of [-2]proPSA and PSA in the first 3 years post-RP, no recent studies exist on the potential use of markers such as fPSA, %fPSA, hK2 and PHI to predict BCR and identify disease persistence (DP) in the postoperative setting.…”

Prognostic and diagnostic value of circRNA expression in prostate cancer: A systematic review and meta-analysis

“…However, tissue biopsy is invasive, and the predicted accuracy of PSA should be furthermore improved. Therefore, PSA has been steadily discouraged from being advised in recent years ( 43 , 44 ).…”