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 ...

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...

This cross-sectional study aimed to investigate the effect of supraclavicular fossa (SCF) radiotherapy volumes as well as patient characteristics and nodal pathology on the development of lymphoedema. Ninety-one women who had received SCF nodal radiotherapy after axillary dissection were evaluated. Lymphoedema was defined by two measurements: limb volume difference 200 mL, or circumference difference 10 cm proximal or distal to the olecranon>2 cm. On univariate analysis, the addition of axillary to SCF radiotherapy, increasing width of the SCF field, increasing age, presence of extracapsular extension of nodal involvement and use of hormone treatment was associated with lymphoedema by either one or both definitions. For both definitions of lymphoedema, on multivariate analysis, increasing nodal radiotherapy volume remained significant (P=0.02 to 0.007), as did increased age (P=0.05 to 0.001). We conclude that conventionally fractionated SCF radiotherapy limited laterally by the coracoid process has a lymphoedema risk similar to that expected from axillary dissection alone and a lower risk than wider SCF fields with or without an axillary boost.

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