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BACKGROUND: The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. OBJECTIVE: To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. DESIGN, SETTING, AND PARTICIPANTS: Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. INTERVENTION: Patients underwent salvage lymph node dissection (LND). MEASUREMENTS: Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. RESULTS AND LIMITATIONS: Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p=0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p=0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR=2.92; p=0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p=0.02), higher number of positive lymph nodes (HR: 1.04; p=0.006), and complete BR to salvage LND (HR: 0.31; p=0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. CONCLUSIONS: Salvage LND is feasible in patients with BCR after RP

PURPOSE: We assessed the value of [(11)C]choline positron emission tomography/computerized tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging. MATERIALS AND METHODS: Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [(11)C]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1) previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%). RESULTS: Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p <0.05). Prostate specific antigen was the only significant predictor of tomography results (p <0.05). CONCLUSIONS: Positron emission tomography/computerized tomography detected increased [(11)C]choline uptake, suggesting recurrent disease in 11% of patients with prostate cancer, increasing prostate specific antigen after radical prostatectomy and no evidence of disease on conventional imaging. This modality may be useful to restage disease but it cannot be used to guide therapy

PURPOSE: Detection of recurrence in prostate cancer patients with biochemical failure after radical prostatectomy by [(11)C]choline PET/CT depends on the prostate-specific antigen (PSA) level. The role of other clinical and pathological variables has not been explored. METHODS: A total of 2,124 prostate cancer patients referred to our Institution for [(11)C]choline PET/CT from December 2004 to January 2007 for restaging of disease were retrospectively considered for this study. Inclusion criteria were: previous treatment by radical prostatectomy, and biochemical failure, defined as at least two consecutive PSA measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary logistic analysis was used to investigate the predictive factors of [(11)C]choline PET/CT. PET/CT findings were validated using criteria based on histological analysis, and follow-up clinical and imaging data. Receiver operating characteristic (ROC) analysis was used to assess the performance of [(11)C]choline PET/CT in relation to PSA levels. RESULTS: The mean PSA level was 3.77 +/- 6.94 ng/ml (range 0.23-45 ng/ml; median 1.27 ng/ml). PET/CT was positive for recurrence in 161 of 358 patients (45%). On an anatomical region basis, [(11)C]choline pathological uptake was observed in lymph nodes (107/161 patients, 66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161 patients, 29%). PET/CT findings were validated using histological criteria (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In multivariate analysis, high PSA levels, advanced pathological stage, previous biochemical failure and older age were significantly (P < 0.05) associated with an increased risk of positive PET/CT findings. The percentage of positive scans was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% i

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]

BACKGROUND: Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES: To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS: From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS: Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS: In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Purpose The accuracy of positron emission tomography (PET)/CT with [11C]choline for the detection of prostate cancer is not well established. We assessed the dependence of [11C]choline maximum standardized uptake values (SUVmax) in the prostate gland on cell malignancy, prostate-specific antigen (PSA) levels, Gleason score, tumour stage and anti-androgenic hormonal therapy. Methods In this prospective study, PET/CT with [11C]choline was performed in 19 prostate cancer patients who subsequently underwent prostatectomy with histologic sextant analysis (group A) and in six prostate cancer patients before and after anti-androgenic hormonal therapy (bicalutamide 150 mg/day; median treatment of 4 months; group B). Results In group A, based on a sextant analysis with a [11C]choline SUVmax cutoff of 2.5 (as derived from a receiver-operating characteristic analysis), PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 72, 43, 64, 51 and 60%, respectively. In the patient-by-patient analysis, no significant correlation was detected between SUVmax and PSA levels, Gleason score or pathological stage. On the contrary, a significant (P < 0.05) negative correlation was detected between SUVmax and anti-androgenic therapy both in univariate (r 2 = 0.24) and multivariate (r 2 = 0.48) analyses. Prostate [11C]choline uptake after bicalutamide therapy significantly (P < 0.05) decreased compared to baseline (6.4 ± 4.6 and 11.8 ± 5.3, respectively; group B). Conclusion PET/CT with [11C]choline is not suitable for the initial diagnosis and local staging of prostate cancer. PET/CT with [11C]choline could be used to monitor the response to anti-androgenic therapy.

BACKGROUND AND PURPOSE: To investigate the usefulness of vesicourethral anastomotic biopsy (VUBx) in patients who are candidates for salvage radiotherapy (SalvRT) after radical prostatectomy (RRP). MATERIAL AND METHODS: From 1992 to 2001, 98 patients with a PSA failure (PSAf) after RRP underwent SalvRT to the prostatic bed (median dose 70 Gy). In 50/98 patients the VUBx was positive, in 26 negative; 22 patients underwent SalvRT without a prior VUBx. The prognostic impact on biochemical disease-free survival (bNEDs) of histologic confirmation of the local failure was evaluated retrospectively. RESULTS: In the 40 patients with pre-RT PSA < or = 0.9 ng/mL, no additional prognostic information derived from the VUBx, while, for higher PSA values, a positive histology resulted as a covariate independently predictive of post-RT outcome (5-year bNEDs: 74% vs 42% in the 35 and 23 patients with a positive or negative/not performed VUBx, respectively, P=.03), together with pT, pre-RT PSA < or = 1.5 ng/mL, and PSA doubling time. CONCLUSIONS: In case of PSAf after RRP, VUBx before SalvRT seems unnecessary for PSA < or = 0.9 ng/mL. For higher values, a positive VUBx seems to always justify a SalvRT, which may not be recommendable, given the nonnegligible risk of an already micrometastatic disease, if the biopsy results are negative.

OBJECTIVES: To prospectively evaluate the accuracy of integrated [(11)C]choline-PET/CT in the diagnosis of lymph-node recurrence in prostate cancer patients with biochemical failure after surgery. METHODS: Since October 2002, 25 patients with biochemical recurrence (median PSA: 1.98ng/ml), based on evidence of lymph-node metastases on [(11)C]choline-PET/CT scan (21 cases) or conventional imaging (4 cases), were scheduled for either bilateral pelvic (12 cases) or both pelvic and retroperitoneal lymph-node dissection (13 patients). RESULTS: Sixty-three nodal sites were evaluated histologically. The mean number of nodes removed and positive nodes were 21.92+/-16.91 (range: 4-74) and 8.84+/-9.65 (range: 1-31), respectively. Of the four patients with negative [(11)C]choline-PET/CT and positive magnetic resonance, none had nodal metastases. Nineteen of the 21 patients (90%) with positive [(11)C]choline-PET/CT had nodal metastases of prostate adenocarcinoma at histologic evaluation. A lesion-based analysis showed that [(11)C]choline-PET/CT sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 64%, 90%, 86%, 72%, and 77%, respectively. The mean maximum diameter of true positive metastases was larger than false-negative ones (15.0 vs. 6.3mm; p=0.0004). CONCLUSIONS: [(11)C]Choline-PET/CT is an accurate diagnostic tool for the detection of lymph-node metastases of recurrent prostate cancer. The low negative predictive value seems to depend on the limited capability of [(11)C]choline-PET/CT to detect microscopic lesions. The high positive predictive value, even with low PSA values, provides a basis for further treatment decisions.

In the long-term there is biochemical evidence of recurrent prostate carcinoma in approximately 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables, e.g. Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of prostate-specific antigen (PSA) recurrence, may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS-guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumour mass at very low PSA levels (< 1 ng/mL) TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral anastomosis remains unclear. However, 111In-capromab pendetide scintigraphy and [11C]-choline tomography (which are better than conventional imaging for detecting metastatic tumour), have low detection rates for local disease and are considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of < 1 ng/mL, Gleason score < 8 and radiation dose of 66-70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need to take a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA-only progression after RP remains in question.