68Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy.

OBJECTIVES: The primary objective was the evaluation of Gallium 68 (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PET/CT) detection rate, for identifying the site of prostate cancer (PCa) relapse (local vs systemic), stratifying the population according to different clinical stages of biochemical recurrence (BCR). Secondary aims were: 1) to evaluate the association of clinical/pathologic features and 68Ga-PSMA-11 PET/CT detection rate, 2) to compare 68Ga-PSMA-11 PET/CT with other imaging procedures, and 3) to evaluate the positive predictive value (PPV) in a per-patient analysis. MATERIAL AND METHODS: This population was enrolled through a prospective, open label, single-center trial performed at the Nuclear Medicine of the University Hospital of Bologna (Eudract: 2015-004589-27 OsSC). The inclusion criteria were: (1) proven PCa, (2) surgery or radiotherapy as definitive therapy, (3) proven BCR, (4) prostate-specific antigen (PSA) 0.2-2 ng/ml, (5) age ≥ 35 years, and 6() willing to sign an informed consent. Three-hundred and thirty-two (332) patients were enrolled between March 2016 and June 2017; mean/median PSA was 0.84/0.61 ng/ml, 97.9% (325/332) of patients received radical prostatectomy and 2.1% (7/332) radiotherapy. Different patterns of BCR were identified by referent physicians as follows: (a) persisting detectable PSA after radical prostatectomy in 13.5% (45/332) of patients (subgroup 1), (b) first-time PSA failure after radical therapy in 44.9% (149/332) (subgroup 2), and (c) PSA increase after salvage or hormonal therapy in 41.6% (138/332) (subgroup 3). RESULTS: Primary objective: 68Ga-PSMA-11 PET/CT detection rate was 53.6% (CI 95% 48.1%-59.1%). In a patient-based analysis, disease confined to pelvis (prostate bed and/or lymph-nodes) was detected in 24.7% of cases (82/332). The presence of at least one distant lesion was observed in 28.9% of cases (96/332). The detection rate in different subgroups was: subgroup 1 = 64.5%, subgroup 2 = 45.6%, and subgroup-3 = 58.7%. Secondary objectives: 1) PSA (p = 0.041) and PSAdt (p = 0.001) showed association with 68Ga-PSMA-11 PET/CT detection rate, and 2) correlative imaging was available in 73.2% of patients (243/332). When 68Ga-PSMA-11 PET/CT was positive, correlative imaging resulted negative in 83% of cases (108/130). 3) The calculated PPV was 96.2%. CONCLUSION: Our data confirmed the efficacy of 68Ga-PSMA-11 PET/CT for detecting local vs systemic disease in PCa patients presenting PSA failure after radical therapy. Furthermore, 68Ga-PSMA-11 PET/CT detection rate is different depending on the clinical stage of BCR, and this information should be taken into consideration by referring physicians.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy.

PURPOSE: The primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy. METHODS: 68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2-0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images. RESULTS: We enrolled 119 PCa patients (mean age 66 years, range 44-78 years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20-0.50 ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result. CONCLUSION: In our patient series with PSA levels <0.5 ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

The role of 18F-FDG PET/CT in the detection of osteosarcoma recurrence.

AIM: The aim of this study was to investigate the diagnostic accuracy of 18F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy. METHODS: Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) 18F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of 18F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). 18F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated. RESULTS: 18F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis 18F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after 18F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively. CONCLUSION: 18F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

(11)C-Choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel.

PURPOSE: To investigate the role of (11)C-choline PET/CT for evaluating the response to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel in comparison with PSA response. METHODS: Inclusion criteria were (a) proven mCRPC, (b) docetaxel as first line of chemotherapy (docetaxel 75 mg/m(2) + prednisone 5 mg), and (c) (11)C-choline PET/CT and PSA values assessed before and after docetaxel administration. A total of 61 patients were retrospectively enrolled (mean age 68.9 years, range 57 - 84 years). (11)C-Choline PET/CT was performed at baseline before docetaxel treatment (PET1) and after the end of treatment (PET2). PSA values were measured before treatment (PSA1) and after treatment (PSA2). PET2 was reported as complete response (CR), partial response (PR) or stable disease (SD). Progressive disease (PD) was considered if a new lesion was seen. PSA trend was calculated from the change in absolute values between PSA1 and PSA2. A decrease of ≥50 % between PSA1 and PSA2 was considered a PSA response. Clinical, radiological and laboratory follow-up ranged from 6 to 53 months (mean 13.5 months). RESULTS: Of the 61 patients, 40 (65.5 %) showed PD on PET2, 13 (21.3 %) showed SD, 2 (3.4 %) showed PR, and 6 (9.8 %) showed CR. An increasing PSA trend was seen in 29 patients (47.5 %) and a decreasing PSA trend in 32 patients (52.5 %). A PSA response of ≥50 % was seen in 25 patients (41 %). Radiological PD was seen in 23 of the 29 patients (79.3 %) with an increasing PSA trend, in 16 of the 32 patients (50 %) with a decreasing PSA trend, and in 11 of the 25 patients (44 %) with a PSA response of ≥50 %. In the multivariate statistical analysis, the presence of more than ten bone lesions detected on PET1 was significantly associated with an increased probability of PD on PET2. No association was observed between PSA level and PD on PET2. CONCLUSION: Our results suggest that an increasing PSA trend measured after docetaxel treatment could be considered predictive of PD. In patients with decreasing PSA values (decreasing PSA trend and a PSA response of ≥50 %), (11)C-choline PET/CT may be useful to identify those with radiological progression despite a PSA response. Finally, the tumour burden, expressed as number of bone lesions on PET1, is significantly associated with an increased probability of PD on PET2.

(11)C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series.

PURPOSE: To evaluate (11)C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing (11)C-choline PET/CT during BCR. METHODS: We retrospectively analysed 9,632 (11)C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. RESULTS: Overall, 52.8 % of the (11)C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive (11)C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 (11)C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. CONCLUSION: In a large cohort of patients, the feasibility of (11)C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed.

Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial.

PURPOSE: The aim of this retrospective two-centre study was to investigate the clinical impact of (11)C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer (rPCa) after radical therapy. METHODS: Enrolled in this retrospective study were 150 patients (95 from Bologna, 55 from Würzburg) with rPCa and biochemical relapse (PSA mean ± SD 4.3 ± 5.5 ng/mL, range 0.2-39.4 ng/mL) after radical therapy. The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative androgen deprivation therapy (ADT) in 55 patients. The effective clinical impact of (11)C-choline PET/CT was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. Multivariate binary logistic regression analysis included PSA level, PSA kinetics, ongoing ADT, Gleason score, TNM, age and time to relapse. RESULTS: Changes in therapy after (11)C-choline PET/CT were implemented in 70 of the 150 patients (46.7%). A major clinical impact was observed in 27 patients (18%) and a minor clinical impact in 43 (28.7%). (11)C-choline PET/CT was positive in 109 patients (72.7%) detecting local relapse (prostate bed and/or iliac lymph nodes and/or pararectal lymph nodes) in 64 patients (42.7%). Distant relapse (paraaortic and/or retroperitoneal lymph nodes and/or bone lesions) was seen in 31 patients (20.7%), and both local and distant relapse in 14 (9.3%). A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients (p < 0.05). In multivariate analysis, PSA level, PSA doubling time and ongoing ADT were significant predictors of a positive scan (p < 0.05). In statistical analysis no significant differences were observed between the Bologna and Würzburg patients (p > 0.05). In both centres the same criteria to validate PET-positive findings were used: in 17.3% of patients by histology and in 82.7% of patients by correlative imaging and/or clinical follow-up (follow-up mean 20.5 months, median 18.3 months, range 6.2-60 months). CONCLUSION: (11)C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients. It led to an overall change in 46.7% of patients, with a major clinical change implemented in 18% of patients. Further prospective studies are needed to evaluate the effect of such treatment changes on patient survival.

11C-choline PET/CT detects the site of relapse in the majority of prostate cancer patients showing biochemical recurrence after EBRT.

PURPOSE: The aim of this retrospective study was to evaluate the usefulness and the detection rate of (11)C-choline PET/CT in a population of patients with prostate cancer (PC), exclusively treated with external beam radiotherapy (EBRT) as primary treatment, who showed biochemical relapse. MATERIALS AND METHODS: We enrolled 140 patients showing a serum PSA level >2 ng/mL (mean 8.6 ng/mL, median 5 ng/mL, range 2 - 60 ng/mL). All patients had been treated with EBRT to the prostate gland and prostatic fossa with doses ranging from 70 to 76 Gy in low-risk patients (T1/T2 and/or serum PSA <10 ng/mL) and escalating to >76 Gy (range 76 - 81 Gy) in high-risk patients (T3/T4 and/or serum PSA >10 ng/mL). Of the 140 patients, 53 were receiving androgen deprivation therapy at the time of the scan. All positive (11)C-choline PET/CT findings were validated by transrectal ultrasound-guided biopsy or at least 12 months of follow-up with contrast-enhanced CT, MR, bone scintigraphy or a repeated (11)C-choline PET/CT scan. The relationships between the detection rate of (11)C-choline PET/CT and the factors PSA level, PSA kinetics, Gleason score, age, time to relapse and SUV max in patients with positive findings were analysed. RESULTS: (11)C-Choline PET/CT detected the site of relapse in 123 of the 140 patients with a detection rate of 87.8 % (46 patients showed local relapse, 31 showed local and distant relapse, and 46 showed only distant relapse). In patients with relapse the mean serum PSA level was 9.08 ng/mL (median 5.1 ng/mL, range 2 - 60 ng/mL), the mean PSA doubling time was 5.6 months (median 3.5 months, range 0.4 - 48 months), and the mean PSA velocity was 15 ng/mL/year (median 8.8 ng/mL/year, range 0.4 - 87 ng/mL/year). Of the 123 patients with relapse, 77 (62.6 %) showed distant relapse with/without local relapse, and of these 77, 31 (40.2 %) showed oligometastatic disease (one or two distant lesions: lymph node lesions only in 16, bone lesions only in 14, and lymph node lesions and bone lesions in 1). In univariate and multivariate analyses PSA kinetics was the only variable affecting (11)C-choline PET/CT detection rate. A significant correlation between PSA kinetics and site of recurrence (local relapse only vs. distant metastasis) was also observed. CONCLUSION: The detection rate of (11)C-choline PET/CT in patients with PC showing biochemical recurrence after EBRT as primary treatment is relatively high (87.8 %). (11)C-Choline PET/CT was able to detect extraprostatic disease in the 62.6 % of patients. Considering this high detection rate, (11)C-choline PET/CT could have clinical usefulness in the management of these PC patients, but this should be confirmed in future studies.

High Prognostic Value of 68Ga-PSMA PET/CT in Renal Cell Carcinoma and Association with PSMA Expression Assessed by Immunohistochemistry.

In oligo-metastatic renal cell carcinoma (RCC), neither computed tomography (CT) nor bone scan is sensitive enough to detect small tumor deposits hampering early treatment and potential cure. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the neo-vasculature of numerous malignant neoplasms, including RCC, that can be targeted by positron emission tomography (PET) using PSMA-targeting radioligands. Our aim was to investigate whether PSMA-expression patterns of renal cancer in the primary tumor or metastatic lesions on immunohistochemistry (IHC) are associated with PET/CT findings using [68Ga]-PSMA-HBED-CC (PSMA-PET/CT). We then analyzed the predictive and prognostic role of the PSMA-PET/CT signal. In this retrospective single-center study we included patients with renal cancer submitted to PSMA-PET/CT for staging or restaging, with tumor specimens available for PSMA-IHC. Clinical information (age, tumor type, and grade) and IHC results from the primary tumor or metastases were collected. The intensity of PSMA expression at IHC was scored into four categories: 0: none; 1: weak; 2: moderate; 3: strong. PSMA expression was also graded according to the proportion of vessels involved (PSMA%) into four categories: 0: none; 1: 1-25%; 2: 25-50%; 3: >50%. The intensity of PSMA expression and PSMA% were combined in a three-grade score: 0-2 absent or mildly positive, 3-4 moderately positive, and 5-6 strongly positive. PSMA scores were used for correlation with PSMA-PET/CT results. Results: IHC and PET scans were available for the analysis in 26 patients (22 ccRCC, 2 papillary RCC, 1 chromophobe, 1 "not otherwise specified" RCC). PSMA-PET/CT was positive in 17 (65%) and negative in 9 patients (35%). The mean and median SUVmax in the target lesion were 34.1 and 24.9, respectively. Reporter agreement was very high for both distant metastasis location and local recurrence (kappa 1, 100%). PSMA-PET detected more lesions than conventional imaging and revealed unknown metastases in 4 patients. Bone involvement, extension, and lesion number were greater than in the CT scan (median lesion number on PET/CT 3.5). The IHC PSMA score was concordant in primary tumors and metastases. All positive PSMA-PET/CT results (15/22 ccRCC, 1 papillary cancer type II, and 1 chromofobe type) were revealed in tumors with strong or moderate PSMA combined scores (3-4 and 5-6). In ccRCC tissue samples, PSMA expression was strong to moderate in 20/22 cases. The SUVmax values correlated to the intensity of PSMA expression which were assessed using IHC (p = 0.01), especially in the ccRCC subgroup (p = 0.009). Median survival was significantly higher in patients with negative PSMA-PET/CT (48 months) compared to patients with a positive scan (24 months, p= 0.001). SUVmax ≥ 7.4 provides discrimination of patients with a poor prognosis. Results of PSMA-PET/CT changed treatment planning. Conclusions: in renal cancer, positive PSMA-PET/CT is strongly correlated to the intensity of PSMA expression on immunohistochemistry in both ccRCC and chromophobe cancer. PSMA-PET/CT signal predicts a poor prognosis confirming its potential as an aggressiveness biomarker and providing paramount additional information influencing patient management.

Platypnea-orthodeoxia after fibrotic evolution of SARS-CoV-2 interstitial pneumonia. A case report.

Platypnea-orthodeoxia syndrome (POS) is a clinical entity characterized by positional dyspnoea (platypnea) and arterial desaturation (orthodeoxia) that occurs when sitting or standing up and usually resolves by lying down. POS may result from some cardiopulmonary disorders or from other miscellaneous aetiologies. We report a case of POS in a patient after fibrotic evolution of SARS-CoV-2 interstitial pneumonia associated with pulmonary embolism. The patient did not have any evidence of an intracardiac/intrapulmonary shunt.

Unknown SARS-CoV-2 pneumonia detected by PET/CT in patients with cancer.

INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: 18F-FDG, 18F-choline (FCH), and 68Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue 18F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2-positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.

SPECT/CT with 99mTc labelled heat-denatured erythrocyte to detect thoracic and abdominal splenosis.

Scintigraphy with 99mTc labelled heat-denatured erythrocyte (DRBC) allows non invasive diagnosis of heterotopic splenic tissue implantation (splenosis) following splenic trauma or surgery. Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) improves diagnostic accuracy of planar imaging through a more precise localization of functional findings. We report about two cases of splenosis occurring many years after splenectomy. 99MTc-DCRBC scintigraphy was used for differential diagnosis of metasttic disease in one case and to assess an incidental finding at bone scan in the second one. SPECT/CT increased specificity of planar imaging, expecially revealing combined (thoracic and abdominal) splenosis.

PET/Computed Tomography in the Individualization of Treatment of Prostate Cancer.

Choline PET/computed tomographic (CT) imaging represents the most diffused PET imaging techniques to investigate patients with prostate cancer (PCa). It may show the site of tumor recurrence in a single step examination, earlier than other conventional imaging techniques. In this context, the availability of a diagnostic test capable of differentiating between potentially curable local recurrence and metastatic disease implying palliative approaches may play an important role in those patients in whom targeted therapies could be performed according to choline PET/CT results. This review analyzes the value of choline PET/CT imaging in the evaluation of treatment of patients with PCa.

11C-choline PET/CT identifies osteoblastic and osteolytic lesions in patients with metastatic prostate cancer.

AIM: The aim of this study was to compare C-choline PET/CT, prostate-specific antigen (PSA), PSA kinetics, and C-choline uptake in recurrent metastatic prostate cancer patients with osteoblastic and osteolytic bone metastases. PATIENTS AND METHODS: We retrospectively analyzed 140 patients with the following criteria: (a) positive bone lesions identified with C-choline PET/CT and validated as true positive by histology (14.2%), correlative imaging (33.4%), or clinical follow-up (52.4%); (b) after radical prostatectomy (67.9%) or primary radiotherapy (22.1%); (c) proven biochemical relapse with rising PSA levels; (d) no chemotherapy, zoledronic acid, or palliative bone external beam radiation therapy previously administrated during biochemical relapse; and (f) asymptomatic for bone pain. Lesions were categorized as osteoblastic, osteolytic, or bone marrow lesions. Patients were divided into osteoblastic and osteolytic patient groups. RESULTS: C-Choline PET/CT detected oligometastatic bone disease (1-3 lesions) in 98 (70%) of the 140 patients and multiple bone lesions in 42 (30%) of the 140 patients. By per-lesion analysis of 304 lesions, there were 184 osteoblastic, 99 osteolytic, and 21 bone marrow lesions.By per-patient analysis, 97 (69.3%) of the 140 patients were in the osteoblastic group, whereas 43 (30.7%) of the 140 patients were in the osteolytic group. Statistically significant differences in SUVmax (P < 0.001), fast PSA doubling time (P = 0.01), and PSA velocity (P = 0.01) were observed between osteoblastic (lower values) and osteolytic (higher values) groups. By multivariate analysis, fast PSA doubling time was a significant predictor for osteolytic lesions. CONCLUSIONS: We demonstrated differences in PSA kinetics and SUVmax between osteolytic and osteoblastic lesions. C-Choline PET/CT may identify patients that could benefit from early targeted therapies, depending on the type of bone lesions expressed.

11C-choline PET/CT for restaging of bladder cancer.

AIM: The aim of this study was to evaluate of C-choline PET/CT in bladder cancer (BC) patients with suspected relapse after primary therapy. METHODS: Twenty-five BC patients with surgery (21 [84%]) or radiotherapy (4 [16%]) with curative intent had PET/CT for suspicion of relapse. Mean TNM was T2b N0 M0 (range, T1a N0 M0 to T4 N2 M0), whereas mean age was 71.3 years (range, 50-85 years). Nine (36%) of 25 were treated with adjuvant or salvage chemotherapy within 6 months before PET/CT. Positive findings were validated by histology or correlative imaging and/or clinical follow-up lasting at least 12 months. Age, TNM, histology, previous chemotherapy, and type of primary treatment were correlated with PET/CT positivity by univariate and multivariate binary logistic regression analysis. RESULTS: C-choline PET/CT was positive in 16 (64%) of 25. Six (37.5%) of 16 were positive in residual bladder/bladder bed, with 2 local false positive (FP) and 1 false negative (FN) on lymph nodes (LNs); 3 of 16 patients had PET-positive LNs with 1 FP; 1 of 16 patients showed distant metastases. Two (12.5%) of 16 had positive residual bladder/bladder bed and locoregional LNs; 1 (6.3%) of 16, residual bladder/bladder bed and bone; metastasis, 1 (6.3%) of 16 residual bladder/bladder bed and lung metastasis; 2 (12.5%) of 16, LN and distant metastasis. Five (56%) of 9 of PET negatives were FN in residual bladder/bladder bed. Eighteen (72%) of 25 were validated by histology, with 7 (18%) of 25 by correlative imaging and/or clinical follow-up. C-choline PET/CT was sensitive, specific, and accurate, with good positive and negative predictive values for local relapse of 66.7%, 84.6%, 76%, 80%, and 73.3% and 90%, 93.3%, 92%, 90%, and 93.3% for LNs and distant relapse, respectively. No FP or FN was detected for distant metastasis. None of the investigated factors were statistically significant. CONCLUSION: C-choline PET/CT is useful for restaging BC suspected of relapse, especially for the evaluation of LN or distant metastases.

11C-choline PET/CT and bladder cancer: lymph node metastasis assessment with pathological specimens as reference standard.

AIM: The aim of this study was to evaluate the potential role of C-choline-PET/CT in nodal assessment in patients with bladder cancer (BCa) using the pathological specimen as reference standard. PATIENTS AND METHODS: Fifty-nine patients with proven BCa were retrospectively enrolled from April 2011 to January 2014 (mean [SD] age, 70.1 [9] years; range 49-85 years). Of 59 patients, 39 (staging group) were referred to C-choline-PET/CT for preoperative lymph node (LN) evaluation before radical cystectomy and extended pelvic LN dissection. Of the 59 patients, 29 (restaging group) had C-choline-PET/CT for suspected BCa relapse after primary radical surgery. In both groups, C-choline-PET/CT findings were correlated with histology. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to assess C-choline-PET/CT feasibility in LN assessment. Age, TNM, histology, and previous chemotherapy were analyzed as additional predictive factors. RESULTS: C-choline-PET/CT overall detection rate was 62.7% (37/59 patients). On a regional-based analysis, C-choline-PET/CT was considered positive for primary cancer and/or local relapse in bladder bed in 54.2% of the patients (32/59). Pathological LN uptake was reported in 23.7% of the patients (14/59) and systemic choline deposit (bone or lung) in 11.8% of the patients (7/59). Considering LN metastasis detection, compared with histological analysis, C-choline-PET/CT showed in the whole population a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 59%, 90%, 71%, 84%, and 81%, respectively. No other investigated factors reached statistical significance. CONCLUSIONS: C-choline-PET/CT may provide additional diagnostic information in preoperative nodal staging of patients with BCa and be considered a useful tool to restage patients with BCa suspected of relapse. Further studies are needed to assess if C-choline-PET/CT could have an influence on survival of patients with BCa.

Early biochemical relapse after radical prostatectomy: which prostate cancer patients may benefit from a restaging 11C-Choline PET/CT scan before salvage radiation therapy?

UNLABELLED: The aim of the study was to assess which factors may influence (11)C-choline PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients listed for salvage radiation therapy (S-RT) in an early phase of biochemical relapse, to select which patients could obtain the most benefit by performing restaging (11)C-choline PET/CT before S-RT. METHODS: The study comprised 605 patients, treated with radical prostatectomy (RP) with curative intent for PCa who showed rising PSA levels after primary therapy and listed for S-RT. Prostate-specific antigen (PSA) values were >0.2 ng/mL and <2 ng/mL (mean, 1.05 ng/mL; median, 1.07 ng/mL; range, 0.2-2 ng/m; SD, ±0.59). All patients were classified as N0 after RP. Seventeen of 605 patients received adjuvant RT together with RP, whereas 148 of 605 patients received androgen-deprivation therapy (ADT) at the time of PET/CT. PSA, PSA kinetics, Gleason score, age, time to biochemical relapse, ADT, and initial tumor stage were statistically analyzed to assess which factor could influence PET/CT positivity and the detection of local versus distant relapse. RESULTS: (11)C-choline PET/CT was positive in 28.4% of patients (172/605). Eighty-three of 605 patients were positive in the pelvis (group A), distant metastasis (group B) were detected in 72 of 605 patients, and local and distant sites of relapse were detected in 17 of 605 patients (group C). At multivariate analysis, PSA, PSA doubling time (PSAdt), and ongoing ADT were significant predictors for positive scan results, whereas PSA and PSAdt were significantly related to distant relapse detection (P < 0.05). At the receiver-operating-characteristic analysis, a PSA value of 1.05 ng/mL and PSAdt of 5.95 mo were determined to be the optimal cutoff values in the prediction of a positive (11)C-choline PET/CT scan, with an area under the curve (AUC) of 0.625 for PSA and 0.677 for PSAdt. CONCLUSION: (11)C-choline PET/CT may be suggested before S-RT during the early phase of biochemical relapse, to select patients who may benefit from this aggressive treatment. Particularly, patients showing fast PSA kinetics or PSA increasing levels despite ongoing ADT should be studied with (11)C-choline PET/CT before S-RT, considering the higher probability to detect positive findings outside the pelvis.