Purpose: We determined how prostate specific antigen (PSA) doubling time changed with time and whether an early measure of doubling time would accurately predict long-term PSA values and clinical outcome in a cohort of patients followed expectantly after radical prostatectomy.
Materials and methods: We analyzed data on 121 patients with PSA recurrence after radical retropubic prostatectomy. Group and individual analyses were performed on 60 patients who met study inclusion criteria. PSA doubling time was calculated and a curve was plotted using logarithmic transformation with linear regression and least squares analysis. In analysis 1 patients were placed into 3 subgroups according to doubling time. Doubling time was calculated per subgroup and the slopes of the aggregate curves were compared to determine how doubling time changed with time. In analysis 2 we calculated early doubling time per patient using only the initial 2 detectable PSA values and compared it with eventual doubling time in each using all PSA values. In addition, we analyzed how doubling time correlated with the clinical course.
Results: Using the group methodology there was no statistically significant acceleration or deceleration with time in doubling time slope in any of the 3 subgroups. On individual analysis we noted a weak correlation of early with eventual doubling time (correlation coefficient 0.69, p = 0.01). In 88% of patients eventual doubling time was not within 10% of early doubling time. Metastasis developed in 60% of patients with an eventual DT of 0 to 6 months, while 80% with an eventual doubling time of 6 to 12 months had no evidence of local or metastatic disease. No patients with an eventual doubling time of greater than 12 months have had metastatic disease and only 4 (16%) had local recurrence, which was treated with radiation therapy. In 8 of the 14 patients (23%) with local recurrence or metastatic disease early doubling time predicted eventual doubling time. Early doubling time was more rapid and slower than eventual doubling time in 5 and 1, respectively, of the remaining cases, which would have placed them in a different subgroup.
Conclusions: On group analysis PSA doubling time appeared to be constant with time and there was no evidence that it accelerated with time in our dataset of PSA recurrence after radical prostatectomy. On individual analysis early doubling time showed a weak but statistically significant correlation with eventual doubling time. However, there was significant inaccuracy when predicting PSA doubling time based on early PSA values in individuals. Generally early projections of doubling time tend to over predict tumor biological aggressiveness, that is local recurrence or metastasis. A need remains for more accurate predictors of the rate of disease progression at initial PSA recurrence to determine accurately early in the clinical course the patients who may benefit from additional therapy. Currently no patient in our study has died of prostate cancer.