Prostate Cancer Relapse Research Articles

Utility of 11C choline PET CT and MRI in relapsed prostate cancer (PC).

e16586 Background: Choline intracellular transport is upregulated in PC, and it is phosphorylated by choline kinase and becomes trapped within PC cells. 11 C Choline has t½ life of 20.4 minutes and emits positrons detectable by PET. Retrospective studies of 11 C choline PET CT in (PC) have been reported. In this original prospective study, we calculated the performance of 11C choline with whole body PET CT and pelvic PET MRI in patients (pts) with biochemical PC relapse. Methods: From November 2014- June 2016, 101 pts with biochemical PC relapse underwent 11C choline PET CT and pelvic PET MRI. Scans were read in blinded fashion. Tissue was obtained from area of 11 C Choline positivity and correlated with scan results. Results: Sixty-two pts (61%) were included in the analysis. 49 pts were excluded due to non-compliance with protocol. 11C choline PET CT and pelvic MRI showed a sensitivity of 92.5%, specificity of 45.5%, positive predictive value of 75.5%, and negative predictive value of 76.9%. Of 37 pts with positive 11C choline PET scans and confirmation of PC, 12 (32%) had positive 11C choline PET scans and negative CT and MRI scans; 7 (18%) had positive C11 choline and CT scans and negative MRI scans; 12 (32%) had positive 11C choline and MRI scans and negative CT scans, and 9 (24%) had positive 11C choline, CT and MRI scans. Mean PSA level in this group of 37 pts was 9.86 ng/mL (range 0.4 – 107.9 ng/mL), and 7 (19%) of the pts had PSA levels < 2 ng/mL. Conclusions: 11C choline PET improves detection of relapsed PC over CT and MRI scans. 11C choline PET pelvic MRI improves detection over 11C choline PET CT.

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.

e14634 Background: Introducing amino acid sequence changes in highly expressed self-antigens for prostate cancer (PCa) patients (pts) might lead to avoidance of immune tolerance. We evaluated a DNA vaccine (INO-5150) including SynCon PSA and PSMA. Administration of INO-5150 to PCa pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) is postulated to break tolerance, resulting in antigen-specific immune responses which could lead to stabilization of disease progression. Methods: Phase I, open-label, multicenter study of PCa pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSADT > 3 months, testosterone > 150 ng/dL, no concomitant androgen deprivation therapy and no evidence of metastases within 12 months. We evaluated safety, tolerability and for efficacy signals. INO-5150 low (2 mg, arms A and C) or high (8.5 mg, arms B and D) dose with or without INO-9012 (1 mg) was administered IM followed by EP in total 4 dosing arms on Day 0 and at Wks 3, 12, and 24 in 60 planned pts (15/arm). Pts were followed for 72 Wks. Results: 62 pts, 16 each in arms A and D and 15 in B and C were enrolled. Median age: 69.5 yrs (range 55.4-87.7), Gleason score: 7 (5-10), time from initial diagnosis: 8.2 yrs (0.5-23.8) and ECOG PS: 0 (0-1). As of data cutoff of 23Jan17, 52 pts had EOT visit, 7 withdrawn from treatment and 6 (10%) reported disease progression, 3 biochemical and 3 radiographic. Median serum PSA at enrollment was 4.6 ng/mL (range 1.2, 113.7) and at EOT was 6.5 ng/mL (0.1, 73.6). Median PSADT at enrollment was 8.7 months (3.1, 218.1) and at EOT it was 3.1 months (-23.1, 100.0). Safety: no reports of Grade 4-5 SAEs. 6 Grade 3 SAEs in 5 pts: presyncope, cardiac disorder, fall, neoplasm, ALT and AST elevation. Grade 1-3 AEs reported in 51 (82%) pts: 12 (75%) in Arm A, 13 (87%) B, 13 (87%) C, and 13 (81%) in D. Common AEs were injection site pain (24/39%), swelling (14/23%), erythema (14/23%), all Grade 1-2. Conclusions: INO-5150 (+) and (-) INO-9012 was generally safe and well-tolerated at all 4 dose levels in this patient population. Preliminary data suggest PSA stabilization in some patients. Immune analyses are ongoing. (NCT02514213) Clinical trial information: NCT02514213.

Effect of PectaSol-C modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in patients (pts) with nonmetastatic, biochemically relapsed prostate cancer (BRPC): Results of the interim analysis of a prospective phase II study.

e16588 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Preliminary pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day. Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 months (mos), were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. We report here first results of a pre-planned interim analysis after ≤ 50% of planned enrolled pt completed 6 mos of tx. Results: The study was initiated in June 2013. We report here the 6 mos data of the first 35 pts enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analysed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mo, and entered into the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). A future final report will include full tx data (18 mos) and correlative analysis. Conclusions: The interim analysis of the present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Final analysis is pending. Clinical trial information: NCT01681823.

EP-1321: Salvage Radiotherapy in locoregional macroscopically relapsed Prostate cancer:retrospective analysis

EP-1321: Salvage Radiotherapy in locoregional macroscopically relapsed Prostate cancer:retrospective analysis

Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients with negative or inconclusive [18F]Fluoroethylcholine-PET/CT.

[18F]fluoroethylcholine (18FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the 68Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive 18FECH-PET/CT. In this retrospective study 16 men with biochemical PCa relapse and negative (n=14) or inconclusive (n=2) 18FECH-PET/CT underwent whole-body 68Ga-RM2-PET/CT. Mean time from 18FECH-PET/CT to 68Ga-RM2-PET/CT was 6.1±6.8months. Primary therapies in these patients were radical prostatectomy (n=13; 81.3%) or radiotherapy (n=3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to 68Ga-RM2-PET/CT imaging. Mean±SD PSA at 68Ga-RM2-PET/CT was 19.4±53.5ng/ml (range 1.06-226.4ng/ml). 68Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n=4), lymph node metastases (LNM; n=4), bone metastases (n=1) and lung metastasis with hilar LNM (n=1). Seven of ten positive 68Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n=2), by response to site-directed therapies (n=2) or by further imaging (n=3). Patients with a positive 68Ga-RM2-scan showed a significantly higher median PSA (6.8ng/ml, IQR 10.2ng/ml) value than those with a negative scan (1.5ng/ml, IQR 3.1ng/ml; p=0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease. Even in this highly selected population of patients with known biochemical recurrence but negative or inconclusive 18FECH-PET/CT, a 68Ga-RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases. Thus, 68Ga-RM2-PET/CT deserves further investigation as a promising imaging modality for imaging PCa recurrence.

68Ga-PSMA Ligand PET/CT-based Radiotherapy for Lymph Node Relapse of Prostate Cancer After Primary Therapy Delays Initiation of Systemic Therapy

To evaluate 68Ga-PSMA ligand positron-emission tomography-computed tomography (PET/CT)-based radiotherapy for lymph node metastases of prostate cancer after primary therapy. Twenty-three patients received radiotherapy for PSMA ligand-positive lymph node metastases. The median follow-up time was 12.4 (range=6.0-28.5) months. The median pre-treatment prostate-specific antigen (PSA) decreased from 2.75 (range=0.52-8.92) ng/ml to a nadir of 1.37 (range=0.11-8.00) ng/ml (p=0.001) following radiotherapy. Except for one patient (4.4%), PSA level decreased in 22 patients (95.6%). The biochemical failure-free survival and time to initiation of systemic therapy at the median follow-up were 95.6% and 100%, respectively. Three patients (12.9%) presented with recurrent disease outside the initial radiation field. No grade III acute toxicities or late grade II toxicities were observed. 68Ga-PSMA ligand PET/CT-based radiotherapy is a promising local treatment option for isolated lymph node metastases of prostate cancer.

A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.

80 Background: Introducing amino acid sequence changes in highly expressed self-antigens for androgen sensitive prostate cancer pts might be sufficient to break tolerance, thus a DNA vaccine was developed using SynCon PSA and PSMA (INO-5150) that share 96.8 and 91.6% sequence identities to these native antigens, respectively. Administration of these antigens to prostate cancer pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) using the CELLECTRA5P device is postulated to break tolerance, resulting in an antigen-specific immune response which could lead to stabilization of disease progression. Methods: This Phase I, open-label, multicenter study included prostate cancer pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSA doubling time > 3 months, testosterone > 150 ng/dL and no evidence of metastasis within 12 months. INO-5150 with or without INO-9012 was administered IM followed by EP in 4 arms: low (2 mg) or high dose (8.5 mg) INO-5150 alone or with 1 mg INO-9012 on Day 0 and at week 3, 12, and 24 in 60 planned pts (15 pts/arm). DLT assessments were performed after dosing of the first 3 pts of each arm at Week 4. Results: Enrollment is complete in all 4 arms and at data cut-off (10Oct16), 62 enrolled pts received at least one, 60 pts received 3 and about half, 28 pts (10 in arm A, 8 in B, 7 in C, and 3 in D) received all 4 vaccinations. Safety: there were no DLTs noted. Four pts had five Grade 3 SAEs noted as pre-syncope, cardiac disorder, hospitalization for fall, ALT and AST elevation. No Grade 4-5 AEs were noted. Grade 1-3 treatment-emergent AEs occurred in 50 (81%) pts: 12 (75%) in arm A, 13 (87%) B, 13 (87%) C, and 12 (75%) in D. The most common AEs were injection site pain (24/39%), erythema (13/21%), swelling (12/19%), bruising (10/16%), hyperglycemia (8/13%) and fatigue (6/10%), all Grade 1-2. Assessments of immunological response, PSA kinetics and correlation with clinical outcome are ongoing and will be presented. Conclusions: INO-5150 (+) or (-) INO-9012 is generally safe and well-tolerable at all 4 dose levels in a biochemically relapsed prostate cancer patient population. Clinical trial information: NCT02514213.

Stereotactic body radiotherapy for patients with relapsing prostate cancer with bones or nodes oligometastases.

263 Background: To analyze patients treated by stereotactic body radiotherapy (SBRT) for node or bone oligometastatic recurrence of a prostate cancer previously locally treated, To identify possible pronostic factors of early biochemical failure (BF) after SBRT. Methods: We reviewed patients with a rising PSA treated by SBRT between November 2011 and April 2016 for bone or node oligometastases, diagnosed on a 18F Fluorocholine positron emission tomography-computed tomography (PET-CT) following biochemical failure of a prostate cancer after a local curative treatment. Recurrence-free survival (RFS) was the primary end-point defined as the time interval between SBRT and biochemical failure. Biochemical failure was defined as 2 consecutive elevations of PSA with last dosage superior to PSA dosage before treatment, or clinical failure. PSA value before SBRT, location of metastases, number of lesions treated, concomitant androgen deprivation therapy were analyzed to identify pronostic factors of poor response to SBRT. Results: With a median follow-up from time of SBRT of 12 months, we treated 40 patients and 56 metastatic lesions, with a local-control rate of 85%. 19 patients were treated for 1 to 3 bone lesions and 21 patients for 1 to 3 node lesions. 8 patients with bone oligometastases and 13 patients with node oligometastases had a recurrence (p=0.55). The main sites of failure after SBRT were lymph nodes only (7 ; 33%), bone only (7 ; 33 %), and synchronous node and bone (4 ; 19%). A 2nd and 3rdcourse of radiotherapy was delivered in 8 and 1 patients. Median RFS was 345 days (134-426) in the node SBRT group and 494 days (85-877) in the bone SBRT group (p=0.27). On bivariate analysis, a PSA nadir up to 0.51 ng/mL after SBRT was identified as a pronostic factor of a worse RFS (p=0.0038). This result was not confirmed in multivariate analysis (p=0.87). Conclusions: SBRT for node oligometastases showed a non significant lower rate of RFS when compared to SBRT in bone oligometastases. A larger cohort with a longer follow up is needed to determine whether node and bone oligometastases have similar outcomes after SBRT.

The role of PSMA PET/CT imaging in restaging of prostate cancer patients with low prostate-specific antigen levels

Prostate-specific membrane antigen (PSMA) is increasingly being recognized as a novel target for the PET imaging of prostate cancer (PCa) and Ga-DKFZ-11 (Ga-PSMA) has been suggested as a novel tracer for detection of PCa relapses and metastases. The aim of this study was to evaluate the diagnostic value of PSMA PET/CT in the diagnosis of recurrent PCa with low prostate-specific antigen (PSA) levels. We carried out a retrospective analysis of patients who underwent PSMA PET/CT from November 2013 to December 2014 in our department. Among these patients, 50 out of 178 who had increasing PSA levels (<5 ng/ml) and did not have known metastasis were included in this study. Patients had an average PSA of 1.41 ng/ml. A total of 29 patients (58%) showed at least one positive lesion. PET positivity rates of 31% (n=4), 54% (n=13), and 88% (n=14) were observed in patients with a PSA level of less than 0.2, 0.2-2, and 2-5 ng/ml, respectively. A positive correlation was observed between positivity rate and Gleason scores and blood PSA levels. Verification was performed in 46 patients, with biopsy (n=3) and follow-up, and conventional imaging studies at the time of the PET/CT or during follow-up with a mean period of 10.6±3.3 months and ranged from 3.8 to 16.4 months. According to patient-based analysis of 46 cases, 57% of patients had true positive, 24% of patients had true negative, 2% of patients had false positive, an 18% of patients had false-negative findings. A sensitivity of 76.47% (95% confidence interval: 58.83-89.25%) and a specificity of 91.67% (95% confidence interval: 61.52-99.79%) were found. PET/CT with Ga-PSMA is a valuable tool for assessing recurrence of PCa with a high sensitivity in patients who have PSA levels between 0.2 and 5 ng/ml. In addition, this study suggests that PSMA PET/CT can be used in patients with very low (<0.2 ng/ml) but increasing PSA levels, which, in many cases, may influence further clinical management.

Whole pelvis radiotherapy for pathological node-positive prostate cancer : Oncological outcome and prognostic factors.

The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors. All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at asingle tertiary care center were evaluated. A total of 154patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2-3years of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors. Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5years. Median follow-up was 55months (interquartile range 25-87). Multivariate analysis identified having only 1positive lymph node, ashorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17-1.54) and OS (HR 1.22, 95% confidence interval 1.10-1.36). Bone metastases were the most frequent location of PCa relapse (n= 32, 64%). Patients with pN1 PCa treated with wpRT and 2-3years ADT have an encouraging 5‑year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

Normal Uptake of 11C-Acetate in Pancreas, Liver, Spleen, and Suprarenal Gland in PET.

Purpose 11C-Acetate is radiotracer being considered an alternative to 18F-fluorodeoxyglucose. Evaluation of 11C-acetate biodistribution in human parenchymal organs is described. Methods and Materials 60 consecutive patients referred to 11C-acetate PET CT suspected of renal or prostate cancer relapse with negative results (no recurrent tumor) were included in the study. Acquisition from the base of skull to upper thigh was made 20 min after i.v. injection of 720 MBq of 11C-acetate. The distribution was evaluated by measuring the uptake in pancreas (uncinate process and body separately), liver, spleen, and left suprarenal gland. Clinical data of included patients showed no abnormalities in these organs. Results Biodistributions of 11C-acetate radiotracer were compared in different organs. Standardized uptake values of 11C-acetate were significantly higher in pancreatic parenchyma (SUV mean 6,4) than in liver (SUV mean 3,3), spleen (SUV mean 4,5), or suprarenal gland (SUV mean 2,7) tissues. No significant difference was found between pancreatic head (SUV mean 6,4) and body (SUV mean 5,9) uptake. In case of all aforementioned organs, there were no differences either between both sexes or between formerly diagnosed tumors (renal and prostate). Conclusions Evaluation of 11C-acetate uptake differences in parenchymal organs will allow establishing normal patterns of distribution. High pancreatic uptake may be used in quantitative assessment of organ function in diffuse nonneoplastic pathology.

Targeting Stem Cell Protein BMI1; A Potential Therapeutic Approach for Prostate Cancer Therapy

Prostate cancer (CaP) is considered as a vexing challenge for clinical management because of its resistance to the conventional therapies, resulting in most deaths from this disease. The current treatment options including castration shows minimal effect, as most of the patients develop resistance and relapse of more aggressive Castration Resistant Prostate Cancer (CRPC). BMI1 (B cell-specific Moloney murine leukemia virus integration site 1), an oncogenic member of the polycomb group gene family and a transcriptional repressor has emerged as a key regulator in numerous processes including proliferation, differentiation, senescence, and stem cell renewal. Accumulating evidences have also revealed a relationship between BMI1 expression and the clinical grade/stage, therapy response, and survival outcome in most human malignancies, including Prostate cancer. Therefore, in this review, we provide the significant evidences suggesting the potential of BMI1 as a therapeutic target in the management of prostate cancer.

11C-acetate positron-emission tomography/computed tomography imaging for detection of recurrent disease after radical prostatectomy or radiotherapy in patients with prostate cancer.

To evaluate, in a prospective study, the effectiveness of computed tomography (CT)-matched 11C-acetate (AC) positron-emission tomography (PET) in patients with prostate cancer (PCa) who had prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) or radiotherapy (RT). In 103 relapsing patients after RP (n = 97) or RT (n = 6) AC-PET images and CT scans were obtained. In patients with AC-PET-positive results with localized PCa recurrence, detected lesions were resected and histologically verified or, after local RT, followed-up by PSA testing. Patients with distant disease on AC-PET were treated with androgen deprivation/chemotherapy. Of 103 patients, 42 were AC-PET-positive. PSA levels were <1.0, <2.0 and <4.0 ng/mL in six, 16 and 20 patients, respectively. In 25/42 patients AC-PET suggested lymph node metastases: 16/25 patients underwent surgery (10/16 metastasis, 6/16 inflammation); 9/25 patients underwent RT of lymph node metastases, which was followed by decreasing PSA level. In 17/42 patients who had distant disease, systemic treatment was commenced. Combining patients who underwent surgery and those who underwent RT, 19/25 patients were true-positive in terms of AC-PET (positive predictive value 76%). In 5/19 patients, PSA level was <2.0 ng/mL, in 2/19 patients it was <1.0 ng/mL and in 14/19 patients it was 5.4-23.1 ng/mL. In AC-PET-positive patients after surgery or RT (without androgen deprivation), median (range) time to renewed PSA increase was 6 (5-9) months. Only a minority of patients with relapsing PCa appear to benefit from AC-PET for guiding potential local treatment. False-positive results show that factors other than tumour metabolism induce increased AC uptake. The time free of recurrence after local treatment was shorter than expected.

Amplification of MUC1 in prostate cancer metastasis and CRPC development.

Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues. By analyzing MUC1 mRNA levels and gene copy number (GCN) using the OncomineTM database, elevations in MUC1 mRNA in 82 metastases versus 280 primary PCs and in MUC1 GCN in 37 metastases over 181 primary tumors were demonstrated. Analysis of genomic datasets within cBioPortal revealed increases in MUC1 GCN in 2% (6/333) of primary PCs, 6% (9/150) of metastatic PCs, and 33% (27/82) of CRPCs; in comparison, the respective increase in androgen receptor (AR) GCN was 1%, 63%, and 56%, revealing a specific increase in MUC1 GCN for CRPC. Furthermore, a 25-gene MUC1 network was amplified in 52% of CRPCs compared to 69% of CRPCs displaying increases in an AR co-regulator group. While genomic alterations in the MUC1 network largely overlap with those in the AR group, 18 CRPCs (66.7% being neuroendocrine PC) showed genomic alterations only in the MUC1 network. Moreover, genomic alterations in the MUC1 network correlated with PC relapse. Collectively, our observations suggest a combination therapy involving MUC1-based immunotherapy and androgen deprivation.

Cáncer de próstata: concordancia entre PET 18F-colina y TC en recaída bioquímica

ObjectiveTo establish the concordance between 18-fluor choline positron emission tomography (PET) and computed tomography (CT) for re-staging patients with biochemical relapse of prostate cancer according to the TNM system. Materials and methodsThe medical records of the Molecular Imaging Section were retrospectively reviewed. The TNM classification was established by us for each method, and the Kappa concordance statistic was used to classify the results according to the Landis and Koch proposal. ResultsThe PET-choline reported 19 (59.4%) patients N0 and 13 (40.6%) N1, while CT reported 28 (87.5%) N0 and 4 (12.5%) N1. In metastasis classification PET-choline established M0 in 17 (53.1%) patients, M1a in 1 (3.1%), M1b in 5 (15.6%), M1c in 1 (3.1%), M1a+M1b in 7 (21.9%), and M1b+M1c in 1 (3.1%). On the other hand, CT was M0 in 23 (71.9%) patients, M1a in 2 (6.25%), M1a+M1b in 2 (6.25%), and M1b+M1c in 5 (15.6%). The correlation between PET-choline and CT in the TNM lymph node and metastasis classifications was 71.88%, with a Kappa of 0.3455 (standard error 0.1336; P=.0049) and 62.5% with Kappa 0.3725 (standard error 0.0847; P=.0001), respectively. DiscussionSeveral studies have shown a high diagnostic accuracy of PET-choline detecting the spread of the disease compared to conventional methods. ConclusionThere is poor concordance for metastatic and lymph node classifications according to the TNM system between choline-PET and CT.

Rapidly changing landscape of PET/CT imaging in prostate cancer.

PET/CT imaging in men with prostate cancer (PCa) is rapidly growing as clinicians are becoming aware of its possible fundamental role in the diagnostic flow chart of these patients. As this technology becomes more available worldwide, a considerable number of scientific studies are focusing on specific clinical scenarios and novel PET radiopharmaceuticals that might assist improving early diagnosis and shifting to a truly tailored treatment for PCa. This review focuses on the most recent and important publications in PET/CT imaging of PCa. Choline, radiolabelled with either 11-C or 18-F, is now widely used and has shown good performance in detecting sites of disease compared with conventional imaging, especially in biochemical recurrence. However, its sensitivity and specificity when PSA values are low, and especially below 1.0 ng/ml, is insufficient. More recently, a number of new tracers have been proposed for clinical practice. Among them, 68-Ga Prostate-specific membrane antigen have shown so far the most promising results and is replacing choline PET in centres where it is available. It is particularly useful for detecting PCa relapse at low PSA values but may also be useful for staging of patients with intermediate or high risk prostate cancer. 18-F fluorodeoxyglucose PET/CT remains useful for a limited number of patients with PCa and may provide useful prognostic information. PET/CT is a reliable technique in the diagnostic work-up of patients with PCa, particularly in the setting of biochemical recurrence following previous definitive treatment. The landscape of available radiotracers is changing rapidly and includes fluorodeoxyglucose, sodium fluoride, choline, anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, and prostate-specific membrane antigen. Of these, prostate-specific membrane antigen PET/CT appears the most likely to represent a new gold standard with evidence of clinical utility emerging in a variety of scenarios, including staging and biochemical recurrence.

A Simple PSA-Based Computational Approach Predicts the Timing of Cancer Relapse in Prostatectomized Patients

Recurrences of prostate cancer affect approximately one quarter of patients who have undergone radical prostatectomy. Reliable factors to predict time to relapse in specific individuals are lacking. Here, we present a mathematical model that evaluates a biologically sensible parameter (α) that can be estimated by the available follow-up data, in particular by the PSA series. This parameter is robust and highly predictive for the time to relapse, also after administration of adjuvant androgen deprivation therapies. We present a practical computational method based on the collection of only four postsurgical PSA values. This study offers a simple tool to predict prostate cancer relapse. Cancer Res; 76(17); 4941-7. ©2016 AACR.

NMET, A New Target in Recurrent Cancer.

Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but both ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example, in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prostate cancer therapy may promote the expression of nuclear Met (nMET). We recently found a novel nMET/SOX9/ β-Catenin/AR pathway in relapsed prostate cancer which may contribute to the formation of the feedback loop of AR reactivation via MET/nMET. Emerging evidence suggests the possibility of nMET as a prognostic marker in relapsed cancer. This review summarizes recent findings about nMET and its unique role in recurrent cancer.

PSMA PET/CT imaging and therapy

Prostate-specific membrane antigen (PSMA) is increasingly recognized as a novel target for the PET imaging of prostate cancer (PCa) and 68Ga-DKFZ-11 (68Ga- PSMA) has been suggested as a novel tracer for detection of PCa relapses and metastasis. First human studies of PSMA PET/CT imaging have demonstrated high tracer uptake at the sites of primary tumor and lymph node and bone metastasis in direct correlation with aggressiveness and Gleason scores. PSMA PET/CT seems to be a highly accurate imaging tool for restaging of prostate cancer patients with biochemical recurrence. PSMA PET/CT imaging may be used in order to develop a treatment strategy for recurrent disease even in patients with low PSA levels. As a theranostic approach its counterpart Lu-177 labelled ligands have a potential role for the treatment of castration resistant prostate cancer.

Contemporary Mapping of Post-Prostatectomy Prostate Cancer Relapse with 11C-Choline Positron Emission Tomography and Multiparametric Magnetic Resonance Imaging

We identify sites and patterns of cancer recurrence in patients with post-prostatectomy biochemical relapse using 11C-choline positron emission tomography/computerized tomography and endorectal coil multiparametric magnetic resonance imaging. Between January 2008 and June 2015, 2,466 men underwent choline positron emission tomography for suspected prostate cancer relapse at our institution. Of these men 202 did not receive hormone or radiation therapy, underwent imaging with choline positron emission tomography and multiparametric magnetic resonance imaging, and were found to have disease recurrence. Overall patterns of recurrence were described, and factors associated with local only recurrence were evaluated using univariable and multivariable logistic regression. Median prostate specific antigen at positive scan was 2.3 ng/ml (IQR 1.4-5.5) with a median time from prostate specific antigen relapse to lesion visualization of 15 months (IQR 4.8-34.2). Of these 202 men 68 (33%) exhibited local only, 45 (22%) local plus metastatic and 89 (45%) metastatic only relapse. Pelvic node only relapse was observed in 39 (19%) men. Median prostate specific antigen at positive imaging for patients with local only, metastatic only and local plus metastatic relapse was 2.3, 2.7 and 2.2 ng/ml (p=0.46), with a median interval from biochemical recurrence to positive scan of 33.5, 7.0 and 15.0 months, respectively (p <0.001). On multivariable analysis time from biochemical recurrence to positive imaging was independently associated with local only recurrence (OR 1.10 for every 6-month increase, p=0.012). Combined choline positron emission tomography and multiparametric magnetic resonance imaging evaluation of biochemical recurrence after prostatectomy reveals an anatomically diverse pattern of recurrence. These findings have implications for optimizing the salvage treatment of patients with prostate cancer with relapse following surgery.