In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. 11 C-choline and 18 F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. 68 Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga-N,N′-bis[2-hydroxy-5-(carboxyethyl) benzyl]ethylenediamine-N,N′-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of 68 Ga-PSMA versus 18 F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatec-tomy, radiation treatment, or both and were being considered for targeted therapy. Methods: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. 68 Ga-PSMA, 18 F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. Results: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with 68 Ga-PSMA alone, 11 (42%) with both 18 F-fluoromethylcholine and 68 Ga-PSMA, and only 1 (4%) with 18 F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for 68 Ga-PSMA versus 12.5% for 18 F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for 68 Ga-PSMA versus 31% for 18 F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for 68 Ga-PSMA versus 57% for 18 F-fluoromethylcholine. On lesion-based analysis , 68 Ga-PSMA detected more lesions than 18 F-fluoromethylcholine (59 vs. 29, P , 0.001). The tumor-to-background ratio in positive scans was higher for 68 Ga-PSMA than for 18 F-fluoromethylcholine (28.6 for 68 Ga-PSMA vs. 9.4 for 18 F-fluoromethylcholine, P , 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to 68 Ga-PSMA imaging alone. His-tologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 68 Ga-PSMA-positive lesions were consistent with prostate cancer (68 Ga-PSMA was true-positive). The lesion positive on 18 F-fluoromethylcholine imaging and negative on 68 Ga-PSMA imaging was shown at biopsy to be a false-positive 18 F-fluoromethylcholine finding (68 Ga-PSMA was true-negative). Conclusion: In patients with biochemical failure and a low PSA level, 68 Ga-PSMA demonstrated a significantly higher detection rate than ...

We confirmed the original value of the index tumor volume threshold of 0.5 ml for insignificant prostate cancer, and we demonstrated that clinically insignificant prostate cancer may include index Gleason score 6, pT2 tumors with volumes up to at least 1.3 ml. These results suggest a reconsideration of current methods and nomograms used for pretreatment risk assessment.

Objectives To examine the detection rates of 68Ga‐PSMA‐positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management. Materials and Methods A total of 300 consecutive patients with prostate cancer (PCa) who underwent 68Ga‐PSMA‐PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan‐I) database. For the present analysis, we included patients with BCR (prostate‐specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito‐Urinary Group (FROGG) guidelines. Two readers assessed each 68Ga‐PSMA‐PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological 68Ga‐PSMA uptake was investigated, and detection rates were determined according to PSA level. Results A total of 70 patients were included, and 53 positive 68Ga‐PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05–0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1–0.19 ng/mL, 23%; PSA 0.2–0.29 ng/mL, 58%; PSA 0.3–0.49 ng/mL, 36%; and PSA 0.5–0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological 68Ga‐PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the 68Ga‐PSMA findings there was a major management change in 20 (28.6%) patients. Conclusions 68Ga‐PSMA appears to be useful for re‐staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to 68Ga‐PSMA findings.

In patients with intermediate- to high-risk PCa, 68Ga-PSMA PET/CT had a high specificity and a moderate sensitivity for LNM detection. 68Ga-PSMA PET/CT had the potential to replace current imaging for LN staging of patients with PCa scheduled for RP.

ObjectiveTo develop and externally validate a predictive model for detection of significant prostate cancer. Patients and MethodsDevelopment of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. ResultsIn all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. ConclusionsIndividualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of overdetection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.

In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

See an invited perspective on this article on page 1969.68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA # 0.1 ng/mL and .50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% (n 5 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% (n 5 71/99). Forty-five percent (n 5 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% (n 5 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% (n 5 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n 5 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy.Key Words: prostate specific membrane antigen; PSMA; PET/CT; treatment outcome; biochemical failure; post radical prostatectomy J Nucl Med 2017; 58:1972 58: -1976 58: DOI: 10.2967 Radi cal prostatectomy (RP) is the most widely used treatment for men with localized prostate cancer (PC). After surgery, patients are monitored with serial prostate-specific antigen (PSA) measurements. Approximately 20%-50% of pT2-3, node-negative PC patients treated with RP will experience biochemical recurrence, particularly those with poorly differentiat...

ObjectiveTo evaluate the ability of prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET)/computed tomography (CT) to detect intermediate-grade intra-prostatic prostate cancer (PCa), and to determine if PSMA-PET improves the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI). Patients and MethodsA total of 56 consecutive patients with International Society of Urological Pathology (ISUP) grade 2-3 PCa after radical prostatectomy, who underwent both mpMRI and PSMA-PET CT (hereafter PSMA-PET) preoperatively, were enrolled in this study. The accuracy of PSMA-PET, mpMRI alone, and the two procedures in combination was analysed for identifying ISUP grades 1-3 within a 12-segment model. The accuracy of a combined predictive model (PSMA-PET and mpMRI) was determined. Receiver-operating characteristic curve analysis to determine the optimal standardized uptake value (SUV max ) for PSMA-PET in discriminating between ISUP grades 1 and ≥2 was performed. ResultsOn a per-patient basis, the sensitivities for PSMA-PET and mpMRI in identifying ISUP grades 2-3 PCa were 100% and 97%, respectively. Assessing ISUP grade ≥2 PCa using a 12segment analysis, PSMA-PET demonstrated greater diagnostic accuracy (area under the curve), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), with values of 0.91, 88%, 93%, 95% and 85%, respectively, than did mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3-5), at 0.79, 68%, 91%, 87%, and 75%, respectively. When used in combination (PSMA-PET and mpMRI PIRADS 4-5), sensitivity, specificity, NPV and PPV were 92%, 90%, 96% and 81%, respectively. The sensitivity for both techniques reduced markedly when assessing ISUP grade 1 PCa (18% for PSMA-PET, 10% for mpMRI). An SUV max value of 3.95 resulted in 94% sensitivity and 100% specificity. ConclusionPSMA-PET is accurate in detecting segments containing intermediate-grade intra-prostatic PCa (ISUP grade ≥ 2), compared with and complementary to mpMRI. By contrast the detection rate for ISUP grade 1 disease for both PSMA-PET and mpMRI was low.