Detection Efficacy of Hybrid (68)Ga-PSMA Ligand PET/CT in Prostate Cancer Patients with Biochemical Recurrence After Primary Radiation Therapy Defined by Phoenix Criteria.

The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA ligand; PSMA is prostate-specific membrane antigen) PET/CT in patients with biochemical recurrent prostate cancer defined by Phoenix criteria after external-beam radiotherapy or brachytherapy as primary treatment. Methods: One hundred eighteen patients with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range, 2.2-158.4 ng/mL; interquartile range, 4.2-10.2 ng/mL) were finally eligible for this retrospective analysis. Seventy-seven and 41 patients had been treated by external-beam radiotherapy or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen-deprivation therapy (ADT) within at least 6 mo before the PET/CT. The detection rates were stratified by PSA. The influence of primary Gleason score and ADT was assessed. Relationships between SUV and clinical as well as pathologic features in patients with positive findings were analyzed using univariate and multivariable linear regression models. Results: One hundred seven of 118 patients (90.7%) showed pathologic findings indicative for tumor recurrence in 68Ga-PSMA ligand PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43), and 96.8% (30/31) for PSA of 2 to <5, 5 to <10, and ≥10 ng/mL, respectively (P = 0.0377). 68Ga-PSMA ligand PET/CT indicated local recurrence in 68 of 107 patients (63.5%), distant lesions in 64 of 107 patients (59.8%), and local recurrence as well as distant lesions in 25 of 107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) versus without ADT (86.3%, P = 0.0381), but independent from primary Gleason score ≥ 8 (92.0%) versus ≤ 7 (90.2%, P = 0.6346). SUVmax and SUVmean were significantly associated with PSA and ADT (P = 0.018 and 0.004 for SUVmax, respectively; P = 0.025 and 0.007 for SUVmean, respectively). Conclusion:68Ga-PSMA ligand PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy. The detection rate was positively associated to increasing PSA as well as concomitant ADT. 68Ga-PSMA ligand PET/CT enables discrimination of local versus metastatic disease and thus might have a crucial impact on further clinical management. A major limitation of this study is the lack of histopathologic proof in most patients.

Einspieler I ，Rauscher I ，Düwel C ，Krönke M ，Rischpler C ，Habl G ，Dewes S ，Ott A ，Wester HJ ，Schwaiger M ，Maurer T ，Eiber M ... -  《-》

(68)Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer.

Akdemir EN ，Tuncel M ，Akyol F ，Bilen CY ，Baydar DE ，Karabulut E ，Ozen H ，Caglar M ... -  《-》

Multiphasic (68)Ga-PSMA PET/CT in the Detection of Early Recurrence in Prostate Cancer Patients with a PSA Level of Less Than 1 ng/mL: A Prospective Study of 135 Patients.

The main objective of this prospective study was to determine the impact of multiphasic acquisition of 68Ga-PSMA PET/CT in the detection of recurrent prostate cancer in the early stage of biochemical recurrence with a prostate-specific antigen (PSA) level of less than 1 ng/mL. Also, 68Ga-PSMA PET/CT positivity was correlated with clinical parameters for the assessment of predictive markers. Methods: A prospective monocentric study was conducted on 135 prostate cancer patients with biochemical recurrence and a PSA level of less than 1 ng/mL. All patients had undergone initial prostatectomy, with additional radiation therapy in 19.3% of patients and androgen-deprivation therapy in 7.4%. The patients underwent dynamic acquisitions from the prostate bed (1-8 min after injection), standard whole-body acquisitions (60 min after injection), and limited-bed-position delayed acquisitions (120-150 min after injection). The studies were reviewed by 2 board-certified nuclear medicine specialists, independently. A combination of visual and semiquantitative analyses and correlation with morphologic (e.g., MRI) or clinical follow-up findings was used for the final interpretation of lesions as benign or malignant. 68Ga-prostate-specific membrane antigen (PSMA) PET/CT positivity was also correlated with primary clinical findings. Results: Incorporating the information from all phases, we were able to detect 116 lesions in 49.6% of patients (22 local recurrences, 63 lymph nodes, and 31 distant metastases). The detection rates were 31.8%, 44.9%, and 71.4% for PSA < 0.2 ng/mL, 0.2 ≤ PSA < 0.5, and 0.5 ≤ PSA < 1, respectively. Additional dynamic or delayed phases resulted in better determination of equivocal lesions and a higher diagnostic performance in 25.9% of patients. Stand-alone dynamic and delayed images led to better interpretation of equivocal findings in the prostate bed (31.4%) and in other lesions (lymph node or bone) (20%), respectively. Conclusion:68Ga-PSMA PET/CT showed promise for early detection of recurrent disease in patients with a PSA level of 0.5-1.0 ng/mL. However, it showed limited value in patients with a PSA level of less than 0.5 ng/mL. Multiphasic 68Ga-PSMA PET/CT led to a better determination of equivocal findings. Although dynamic images may provide helpful information for assessment of the prostate bed, delayed acquisitions seem to have a greater impact in clarifying equivocal findings.

Beheshti M ，Manafi-Farid R ，Geinitz H ，Vali R ，Loidl W ，Mottaghy FM ，Langsteger W ... -  《-》

Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy.

The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of (68)Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2-59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of (68)Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. Two hundred twenty-two (89.5%) patients showed pathologic findings in (68)Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, and 0.2 to <0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in <1, 1 to <2, 2 to <5, and ≥5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in >6, 4-6, and <4 mo, respectively). (68)Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (≤7 vs. ≥8), detection efficacy was significantly increased (P = 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P = 0.0783). Hybrid (68)Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (<0.5 ng/mL), which in many cases can substantially influence the further clinical management.

Eiber M ，Maurer T ，Souvatzoglou M ，Beer AJ ，Ruffani A ，Haller B ，Graner FP ，Kübler H ，Haberkorn U ，Eisenhut M ，Wester HJ ，Gschwend JE ，Schwaiger M ... -  《-》

Treatment Outcomes from (68)Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

68Ga-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 = 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 = 71/99). Forty-five percent (n = 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 = 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 = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n = 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.

Emmett L ，van Leeuwen PJ ，Nandurkar R ，Scheltema MJ ，Cusick T ，Hruby G ，Kneebone A ，Eade T ，Fogarty G ，Jagavkar R ，Nguyen Q ，Ho B ，Joshua AM ，Stricker P ... -  《-》