[-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

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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Both 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.