PSA doubling time for prediction of [(11)C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy

Giampiero Giovacchini, Maria Picchio, Vincenzo Scattoni, Rita Garcia Parra, Alberto Briganti, Luigi Gianolli, Francesco Montorsi, Cristina Messa
European Journal of Nuclear Medicine and Molecular Imaging 2010, 37 (6): 1106-16

PURPOSE: Previous studies have shown that the positive detection rate of [(11)C]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [(11)C]choline PET/CT findings.

METHODS: PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [(11)C]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3-16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [(11)C]choline PET/CT and 200 bootstrap resamples were used for internal validation.

RESULTS: The median PSA was 1.25 ng/ml (range: 0.23-48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97-45.3 months). [(11)C]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [(11)C]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [(11)C]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15-1.78; PSADT: OR = 1.12; 95% CI: 1.04-1.21]. The percentage of patients with positive [(11)C]choline PET/CT was 27% for PSADT >6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT <3 months. The percentage of patients who displayed pathological [(11)C]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT >6 months to 52% for PSADT <3 months. Conversely, patients who displayed pathological [(11)C]choline uptake in the prostatectomy bed were 0% for PSADT <3 months and 17% for PSADT >6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap-corrected predictive accuracy of 81%.

CONCLUSION: Like PSA, PSADT is an independent predictor of [(11)C]choline PET/CT. [(11)C]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [(11)C]choline PET/CT.

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