==inizio objective==

Prostate cancer is one of the most common cancer affecting men [1]. It is a highly heterogeneous disease with some tumors that progress to invasive, life-threatening disease, whereas others stay latent for the remainder of person’s lifetime. Moreover, prostate cancer is characterized by accumulation of multiple alterations across the genome.
The aim of this study is to identify new molecular markers in formalin-fixed paraffin-embedded (FFPE) tissue of primary tumors in castration resistant prostate cancer (CRPC) patients. To reach this objective, we will analyze the copy number variations (CNV) of 43 chromosomal regions linked to tumor aggressiveness and involved in prostate carcinogenesis, progression and metastasis using Multiplex ligation probe amplification (MLPA) approach.

==fine objective==

==inizio methodsresults==

FFPE samples were collected from 38 patients with prostate cancer after biopsy or radical prostatectomy. Participants were enrolled from the Department of Anatomo-pathology of Morgagni Pierantoni Hospital (Forlì, Italy) and Bufalini Hospital (Cesena, Italy). Five μm sections were cut, DNA isolation was performed using QIAamp DNA FFPE tissue kit (Qiagen), according to the manufacturer’s instructions and DNA was quantified by spectrophotometry (NanoDrop ND-1000, Celbio). MLPA analysis (MRC-Holland) was performed using 150 ng of DNA dissolved in 1X TE buffer (Promega) following the manufacturer’s instructions.
CNV analysis of 43 chromosomal regions was performed using X049-A1 Prostate cancer probemix (MRC-Holland) and was evaluated with Coffalyser software. Two different probes that recognize two different sites were used for 7 genes analyzed: PIK3CA, APC, EZH2, PTEN, ERG, TMPRSS2, AR. PTEN exon 4 was excluded from the analysis because it showed to be sensitive to evaporation during PCR reaction.
CNV values >1.3 were considered as amplification while values <0.7 were considered as deletion. ==fine methodsresults== ==inizio results== Copy number variations of 38 patients were analyzed with MLPA kit. Three patients had a Gleason score ≤6, 9 patients had a Gleason score of 7, 12 patients had a Gleason score of 8, 10 patients had a Gleason score of 9, 3 had a Gleason score of 10 and 1 patient had Gleason score unknown. Thirty eight genes were amplified in our case series and 13 presented amplification in > 30% of patients. The 13 genes, in decreasing order of percentages, are reported below: TMPRSS2 exon 6 (63.2%), TMPRSS2 exon 14 (57.9%), RAD21 (52.6%), MYC3 (50%), AR exon 6 (50%), AR exon 2 (42.1%), TCEB1 (39.5%), mir151 (39.5%), ERG exon 14 (36.8%), KIAA0196 (36.8%), MCM7 (36.8%), ZFHX3 (34.2%), ERG exon 6 (31.6%).
Thirty two genes were deleted in our case series and only mir15a presented a loss in 39.5% of patients. Moreover, 7 patients presented TMPRSS2-ERG fusion.
Statistical analysis will be performed to correlate CNV with clinical characteristics of patients.

==fine results==

==inizio discussions==

As androgen steroids play a key role in prostate cancer growth and development, the principal therapeutic approach is androgen-deprivation. However, hormone therapies lead to a decrease in testosterone and dihydrotestosterone (DHT) synthesis and patients with metastatic prostate cancer only benefit temporarily from these therapies, progressing to a castration-resistant status [2].
For this reason it could be important to genetically characterize prostate cancer tissues from CRPC patients to identify those with a worse disease progression.
MLPA analysis allows to perform genetic characterization and for finding new alterations and important variants in paraffin embedded tissues [3]. We found that 13 genes were frequently amplified in our case series (> 30% of patients) and 1 was deleted in about 40% of patients.
The most amplified genes included TMPRSS2, involved in the fusion with ERG that is detected in about half of prostate cancer with favourable prognosis [4], 8q region (RAD21, MYC3, TCEB1 and mir151) that is associated to aggressive behaviour and poor prognosis of prostate cancer [5,6], and AR that is associated to early pathogenesis as well as in progression to advanced stages and mostly found in CRPC [7-9]. Mir15a deletion is associated to cancer progression [10].

==fine discussions==

==inizio conclusion==

Our results revealed that several genomic alterations are common in CRPC patients and they could be crucial to identify more aggressive diseases, characterized by poor prognosis and associated to progression to advanced stages.

==fine conclusion==

==inizio reference==

[1] Tao ZQ, Shi AM, Wang KX, Zhang WD. Epidemiology of prostate cancer: current status. Eur Rev Med Pharmacol Sci. 2015;19:805–12.
[2] Titus MA, Schell MJ, Lih FB, Tomer KB, Mohler JL. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 2005, 11:4653-4657.
[3] Yelensky R, Frampton GM, Park K, Downing SR, MacDonald TY, Jarosz M, Lipson D, Tagawa ST, Nanus DM, Stephens PJ, Mosquera JM, Cronin MT, Rubin MA. Targeted next generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013 May;63(5):920-6.
[4] Saramäki OR, Harjula AE, Martikainen PM, Vessella RL, Tammela TL, Visakorpi T. TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res. 2008 Jun 1;14(11):3395-400.
[5]Ribeiro FR, Jerónimo C, Henrique R, Fonseca D, Oliveira J, Lothe RA, Teixeira MR. 8q gain is an independent predictor of poor survival in diagnostic needle biopsies from prostate cancer suspects. Clin Cancer Res. 2006 Jul 1;12(13):3961-70.
[6] El Gammal AT, Brüchmann M, Zustin J, Isbarn H, Hellwinkel OJ, Köllermann J, Sauter G, Simon R, Wilczak W, Schwarz J, Bokemeyer C, Brümmendorf TH, Izbicki JR, Yekebas E, Fisch M, Huland H, Graefen M, Schlomm T. Chromosome 8p deletions and 8q gains are associated with tumor progression and poor prognosis in prostate cancer. Clin Cancer Res. 2010 Jan 1;16(1):56-64.
[7] Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinänen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet. 1995 Apr; 9(4):401-6.
[8] Koivisto P, Kononen J, Palmberg C, Tammela T, Hyytinen E, Isola J, Trapman J, Cleutjens K, Noordzij A, Visakorpi T, Kallioniemi OP. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res.1997 Jan 15;57(2):314-9.
[9] Grossmann ME, Huang H, Tindall DJ. Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst. 2001 Nov 21;93(22):1687-97.
[10] Porkka KP, Ogg EL, Saramäki OR, Vessella RL, Pukkila H, Lähdesmäki H, van Weerden WM, Wolf M, Kallioniemi OP, Jenster G, Visakorpi T. The miR-15a-miR-16-1 locus is homozygously deleted in a subset of prostate cancers. Genes Chromosomes Cancer. 2011 Jul;50(7):499-509.

==fine reference==

==inizio objective==

In patients affected by bone metastatic castration-resistant prostate cancer (mCRPC) survival is improved by Radium-223 (223Ra). Even if antiandrogen hormonal therapy is maintained, the treatments for CRPC are stopped in patients undergoing 223Ra. The primary prostate tumor could progress during 223Ra treatment period, particularly if hematological toxicity, patients compliance and general status and other factors might limit the early start of further therapy.
The aim of our study was to evaluate in terms of progression, death and treatment withdrawal, the clinical impact of the presence or absence of primary tumor in patients undergoing 223Ra therapy for mCRPC.

==fine objective==

==inizio methodsresults==

We reviewed the clinical data of patients treated with 223Ra for symptomatic mCRPC between January 2016 and July 2017. Written informed consent was obtained. Luteinizing hormone-releasing hormone analogues were continued in all patients. Within 1 month of the planned start of the treatment Technetium-99m bone scan and total-body CT scan were performed. 223Ra was administered at the dose of 55 kBq/kg every 4 weeks for up to six injections. Patients didn’t receive any other anticancer therapy during 223Ra treatment.
Patients were stratified in 2 groups in relation to the presence or absence of the primary prostate tumor.
Discontinuation of Radium-223 depended on: patient’s request, occurrence of CTCAE grade 3 or 4 neutropenia, anaemia or thrombocytopenia longer than 14 days, visceral progression or for a dose delay of more than 4 weeks. The clinical outcomes of the 2 groups were compared in terms of progression, death and treatment withdrawal due to toxicity.

==fine methodsresults==

==inizio results==

The clinical records of 44 consecutive patients were reviewed. Median age was 76 years and median BMI 27,2. The Gleason grade of the prostate tumor was 7 in 11 (25%), 8 in 13(29,5%) and ≥ 9 in 13 (29,5%) patients. In 28 patients (63.6%) the primary prostate tumor did not receive any local treatment while 16 (36.4%) and 5 (11.3%) patients had previously undergone radical prostatectomy or prostate radiotherapy respectively. Twenty-six (59.1%) patients had previously submitted to systemic chemotherapy.
Bone metastases were less than 6 in 9 (20,4%), between 6 and 20 in 10 (22.7%) and more than 20 in 24 (54.5%) patients. 223Ra treatment was discontinued in 17 patients (41%). Out of these 17 patients, 14 (77,7%) had their prostate, previously submitted to radiotherapy in 2 patients. Reasons of discontinuation were: toxicity, progression and other causes in 9 (20,4%), 7 (15,9%) and 1 (2,3%) patients respectively.
Twelve (27.3%) patients progressed, out of them 9 (75%) had their prostate, submitted to previous radiotherapy in 1 case only. Four of the 5 dead patients had their prostate. Although no statistical analysis was performed due to the small patients’ number, our result suggest the relevant prognostic role of the presence/absence of the primary tumor in terms of treatment completion and progression

==fine results==

==inizio discussions==

During 223Ra treatment, in absence of other concomitant anticancer therapy different than androgen deprivation, 78% of the treatment discontinuations and 75% of the clinical progressions were recorded among patients maintaining their prostate.

==fine discussions==

==inizio conclusion==

Our preliminary experience show that the presence of the primary prostate tumor might play a detrimental role in terms of clinical response to 223Ra.

==fine conclusion==

==inizio reference==

Acknowledgments: GSTU Foundation, Palermo, Italy for the laboratory kits supply and the statistical support

==fine reference==

==inizio objective==

An extended Prostate Biopsy (10–12 cores) remains the standard for the initial diagnostic evaluation of a suspicious prostate 1 .The rate of prostate cancer (PCa) detection for a first systematic transrectal ultrasound-guided biopsy (TRUS-GB) is typically 30–50% 2 . Nevertheless, clinically significant PCa can be missed even after several repeat TRUS-GB. Multiparametric MRI (mpMRI) of the prostate is able to detect clinically relevant CaP 3-4 . The ability to visualize suspicious PCa on mpMRI allowed to use images as targets for needle biopsy by incorporating (i.e. fusing) mpMRI into a needle-aiming or targeting method 5 . The aim of the study was to evaluate the utility of still performing random cores during targeted magnetic resonance imaging/ultrasound fusion-guided biopsy (FUS-GB) in the diagnosis of
clinically significant prostate cancer (PCa).

==fine objective==

==inizio methodsresults==

Between November 2013 and May 2017, all men with previous history of negative prostate biopsy with PSA level of 4-20 ng/mL undergone mpMRI and FUS-GB + TRUS random biopsy, were consecutively included in the study. All men underwent a 12 extended-cores protocol plus 2-3 targeted cores on the mpMRI index lesion. The UroStation™ (Koelis, France) and a V10 ultrasound system with an end-fire 3D TRUS transducer were used for the fusion images procedure. We analysed the detection rate of clinically significant PCa with FUS-GB + TRUS random biopsy and the incident of positive biopsy in target cores and in random cores.

==fine methodsresults==

==inizio results==

Two hundred and twenty nine men were included in this multicenter study. The median time between mpMRI and biopsy was 30 days. MpMRI detected at least 1 suspicious area in 165 patients (72%), 2 or more suspicious areas in 64 patients (28%). Overall, 122/229 patients (53.2%) had positive biopsies. Gleason score 3+3 was found in 64 patients (52.4%), Gleason score 3+4 in 31 patients (25.4 %), Gleason score 4+3 in 12 patients (9.8%), Gleason score 4+4 in 15 patients (12.2%). The rate of cores positive for clinically significant cancer in target cores alone was 68 % versus 4 % for standard cores alone (p≤0.001).

==fine results==

==inizio discussions==

In naive patients, ultrasound (US)-guided random biopsy is the standard of care to diagnose a prostate cancer. A transrectal approach is used for most prostate biopsies, although some urologists prefer a perineal approach. Cancer detection rates are comparable with both approaches. Correlation between mpMRI imaging (associating T2-weighted imaging with diffusion-weighted imaging, dynamic contrast-enhanced imaging, and/or H1-spectroscopy) and radical prostatectomy (RP) shows good sensitivity for the detection and localisation of Gleason score > 7 cancers 6-7 . Three methods of MRI guidance are available for targeted prostate biopsy: cognitive fusion, direct MRI-guided biopsy, performed within an MRI tube and software coregistration of stored MRI with realtime ultrasound, using a fusion device 8 . Wegelin O. et al shows that magnetic resonance imaging-guided biopsy detects more clinically significant prostate cancer (PCa) and less insignificant PCa compared with systematic biopsy in men at risk for PCa. MRI-Guided Biopsies (MRI-GB) had similar overall PCa detection rates compared with TRUS-Guided Biopsies, increased rates of csPCa, and decreased rates of insignificant PCa. MRI-Target Biopsy (MRI TB) has a superior overall PCa detection compared with Cognitive-TB. Fusion-TB and MRI-TB appear to have similar detection rates. Head-to-head comparisons of MRI-GB techniques are limited 9 . In a recent systematic review, in patients with previous negative prostate biopsy MRI-GB detected more prostate cancer (46.3% vs 26.6%), more significant prostate cancer (32 % vs 16%) and less non significant prostate cancer (9.5% vs 14.5%) than TRUS, with less number of
biopsies 10 . In our study, target biopsy with fusion MRI-TRUS image registration significantly improved cancer detection over that of systematic transrectal ultrasound-guided biopsy. FUS-GB alone missed only 2% high grade cancers detected by TRUS-GB.

==fine discussions==

==inizio conclusion==

In our experience, MRI/TRUS-fusion targeted biopsies detected more men with clinically significant PCa than standard biopsies. Therefore, it’s reasonable to avoid random cores and perform only target cores. Randomized extended and saturation prostate biopsies ruled in a “past prostate biopsy scenario “. They are still a gold standard, but we can assume that they are quickly going to be forgotten

==fine conclusion==

==inizio reference==

1. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a
systematic review. Eichler K 1 , Hempel S, Wilby J, Myers L, Bachmann LM, Kleijnen J. J Urol
2006 May;175 (5):1605-12.
2. Prostate cancer detection rates in different biopsy schemes. Which cores for which
patients? Cormio L, Scattoni V, Lorusso F, Perrone A, Di Fino G, Selvaggio O, Sanguedolce F,
Bufo P, Montorsi F, Carrieri G. World J Urol 2014;32:341–6.
3. High diagnostic ability of multiparametric magnetic resonance imaging to detect anterior
prostate cancer missed by transrectal 12-core biopsy. Komai Y, Numao N, Yoshida S,
Matsuoka Y, Nakanishi Y, Ishii C, Koga F, Saito K, Masuda H, Fujii Y, Kawakami S, Kihara K. J
Urol 2013; 190:867–73
4. Current clinical guidelines for multiparametric prostate MRI. Barentsz JO, Richenberg J,
Clements R, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012; 22:746–757.
5. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a
systematic review. Moore CM, Robertson NL, Arsanious N, Middleton T, Villers A, Klotz
L, Taneja SS, Emberton M. Eur Urol. 2012.
6. Multiparametric 3T prostate magnetic resonance imaging to detect cancer:
histopathological correlation using prostatectomy specimens processed in customized
magnetic resonance imaging based molds. Turkbey B, Mani H, Shah V, Rastinehad
AR, Bernardo M, Pohida T, Pang Y, Daar D, Benjamin C, McKinney YL, Trivedi H, Chua
C, Bratslavsky G, Shih JH, Linehan WM, Merino MJ, Choyke PL, Pinto PA. J Urol, 2011. 186:
1818.
7. Multifocality and prostate cancer detection by multiparametric magnetic resonance
imaging: correlation with whole-mount histopathology. Le JD, Tan N, Shkolyar E, Lu
DY, Kwan L, Marks LS, Huang J, Margolis DJ, Raman SS, Reiter RE. Eur Urol, 2015. 67: 569.
8. MRI-ultrasound fusion for guidance of targeted prostate biopsy. Marks L, Young S,
Natarajan S. Curr Opin Urol. 2013 Jan;23(1):43-50
9. Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate
Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imaging-transrectal
Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique? Wegelin
O, van Melick HHE, Hooft L, Bosch JLHR, Reitsma HB, Barentsz JO, Somford DM. Eur Urol.
2017 Apr;71(4):517-531.
10. Multiparametric-MRI- Guided Biopsy in the Era of Precision Medicine. Bergero
MA, Martínez PF, Radtke JP, Hadaschik BA. Arch Esp Urol. 2017 Dec;70(10):833-844.

==fine reference==

==inizio objective==

We present our experience with MRI/US fusion biopsy after the first 125 consecutive patients.

==fine objective==

==inizio methodsresults==

We prospectively evaluated the first consecutive 125 patients underwent to TRUS/US fusion biopsy. MRI images were obtained using a 1.5T scanner with a pelvic phased array coil, each suspicious area was further characterized according to the ESUR PI-RADS v.2 global score. All biopsy core specimens were examined by 2 urogenital pathologists and graded according to the 2005 International Society of Urological Pathology Modified Gleason Grading System
Characteristics of the patients: 80 patients with at least 1 negative biopsy (mean previous negative biopsies 1.2, CI 0-3), 32 biopsy-naïve patients, 13 patients on active surveillance. Mean age 66,1 years (CI 48-78), mean PSA= 8,1 ng/ml (CI 3.3- 21); mean Prostate Volume 57,7 ml ( CI 22-140), , DRE positive in 6/125, number of lesions dectected by MRI 1.4 ( 66 PIRADS 3, 54 PIRADS 4, 5 PIRADS 5) mean cores from each MRI target lesion 3 (CI 2-6), mean total cores 15 ( CI 12-19).

==fine methodsresults==

==inizio results==

55/125 positive for PCA (overall detection rate of 44.%). 14/66 positive for PCA in PIRADS 3 patients (detection rate of 21%), 37/54 positive for PCA in PIRADS 4 patients (detection rate of 68%), 4/5 positive for PCA in PIRADS 5 patients (detection rate of 80%).
In biopsy naive patients ( 32 of 125 pts) we obtained a detection rate of 59% (19/32 PCA): 55%(5/14) in pirads 3, 75% in PIRADS 4 (12/16), 100% ( 2/2) in PIRADS 5. Significant PCA in 10/32 ( 31%). 7 significant PCA was detected in target core e 3 in random core. in 8/32 PCA the random mapping was diagnostic ( target negative)
In re-biopsy patients ( 80 of 125 pts) we obtained a detection rate of 33% (27/80 PCA): 14%(7/51) in pirads 3, 69% in PIRADS 4 (18/26), 66% ( 2/3) in PIRADS 5. Significant PCA in 16/32 ( 50%), 14 in target core e 2 in mapping core. in 7/27 PCA the random mapping was diagnostic ( target negative)
In patients on active surveillance ( 13 of 125 pts) we obtained a positive biopsy in 9/13 pts ( 69%): in 5/13 fusion biopsy histology caused the switching to active treatment
The mean time of the procedure was 42 min (C.I. 22-55) in the first 20 patients , 32 min (C.I. 20-42) in the second 20 patients and than 20 min patients (C.I. 16-32)

==fine results==

==inizio discussions==

==fine discussions==

==inizio conclusion==

Our overall detection rate was 44% ( Significant PCA in 31% of Naïve patient and 50% in repeated biopsy).These results are similar to current literature and promising for the future. We believe that using a platforms of co-registered MRI/US fusion biopsy we improved risk stratification and reduced underdiagnosis, understaging, undergrading in biopsy naïve patient, in patients with a previous negative biopsy and persistent suspicion of PCA and in patients on active surveillance. Fusion target biopsy is always associated with random mapping in our experience.

==fine conclusion==

==inizio reference==

==fine reference==

==inizio objective==

We present our technique for “clip-less” antegrade neurovascular bundle preservation during laparoscopic radical prostatectomy, along with the short-term follow up of our patients’ sexual function.

==fine objective==

==inizio methodsresults==

We performed laparoscopic radical prostatectomy using an anterogrady extraperitoneal approach. After splitting and conservation of the bladder neck, the prostate back plane was developed distally to the apex of the prostate in the median line. This plan was completely developed by releasing vascular peduncles and neurovascular bundles in the medial-lateral direction, with occasional use of bipolar cauterion and without the use of clips.

==fine methodsresults==

==inizio results==

A total of 85 patients met these inclusion criteria between
January 2015 and December 2016, with an average follow-up of 6 months. Patients received the International Index of Erectile Function – 5 (IIEF-5) at 1, 3, 6 and 12 months after surgery. The overall score for both unilateral and bilateral nervous groups was 11, 15, 17 and 22 at 1, 3, 6 and 12 months postoperatively, respectively. These coincided with a return to the base power rate of 47%, 54%, 66%, and 69% at 1, 3, 6, and 12 months, respectively.

==fine results==

==inizio discussions==

We are encouraged by our initial results of LERP, which we believe allows a finer dissection with less trauma during nerve preservation. This technique may result in greater preservation of the NVBs, translating to faster and, perhaps, greater recovery of the patient’s sexual function.

==fine discussions==

==inizio conclusion==

Anterograde dissection of the neurovascular bundle, avoiding the use of clip or monopolar cauterization during laparoscopic radical prostatectomy, may result in an early return of sexual function

==fine conclusion==

==inizio reference==

L Salomon,A.G.Anastasiadis,R.Katz,et al.Urinary continence and erectile function:a prospective evaluation of functional results alter radical laparoscopic prostatectomy
Eur Urol,42(2002), pp.338-343

R.KatzL.Salomon,A.Hoznek,et al.Patient reported sexual function following laparoscopic radical prostatectomy
J Urol168(2002), pp.2078-2082

P.C.Walsh,H.Lepor,J.C.EgglestonRadical prostatectomy with preservation of sexual function:anatomical and pathological considerations
Prostate,4(1983), pp.473-485

E.D.Kursh,D.R.BodnerAlternative method of nerve-sparing when performing radical retropubic prostatectomy
Urology,32(1988), pp.205-209

M.S.Litwin,G.Y.Melmed,T.NakazonLife after radical prostatectomy:a longitudinal study
J Urol,166(2001), pp.587-592

==fine reference==

==inizio objective==

The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells and is progressively up-regulated during disease progression, correlating negatively with prognosis [1,2,3].
Due to its selective overexpression in prostate cancer, PSMA has been recognized as a highly promising target for diagnostic and therapeutic applications [4,5,6].
A number of PSMA ligands have been developed for radiolabeling with PET radioisotopes such as 68Ga or 18F which can be used to detect PSMA-expressing Pca [7].
On October 2015 the Prostate Cancer Unit was settled up at the University Hospital of Parma.
Diagnostic and therapeutic workflow of medium/high-risk patients is planned during the multidisciplinary (MD) meeting weekly, and all high-tech diagnostic procedures (PET/CT, echo-fusion biopsy, multiparametric MRI) are decided during the meeting.
In this study we report about impact of PSMA-PET/CT in managing Pca patients in the context of the PCa Unit.

==fine objective==

==inizio methodsresults==

All high-risk patients (pre-therapeutic PSA values above 20 ng/ml, Gleason score 8, persisting PSA values after radical prostatectomy, PSA values before SRT above 2 ng/ml or metastatic regional lymphnodes diagnosed during prostatectomy) were submitted to a pre-therapeutic PSMA-PET/CT. Intermediate risk patients were evaluated for PSMA-PET/CT according to multidimensional assessment, comorbidities, inconclusive conventional imaging for distant metastasis.
Synthesis of [68Ga]-PSMA-HBED-CC was performed using a fully automated module (Scintomics GRP®, Fuerstenfeldbruck, Germany) and 68Ga was obtained from a IGG100 68Ge/68Ga generator (Eckert & Ziegler, E&Z, Berlin, Germany). Our method to assess the radiochemical and chemical purity of [68Ga]-PSMA-HBED-CC was previously validated [8].
PET dynamic images were acquired immediately after i.v. injection of [68Ga]PSMA-HBED-CC (150 MBq) on a hybrid scanner Discovery IQ (GE Healthcare). Whole body PET/CT was acquired in supine position from skull to medium thigh of the femur 60 min after tracer injection. In all patients, a non-diagnostic CT was acquired for attenuation correction.

==fine methodsresults==

==inizio results==

Since 2016 March to 2017 October, we produced 210 batches of [68Ga]PSMA-HBED-CC for 303 patients (RCP% 99.90, Yeald 65.53%). Data have been collected from 198 patients (until June 2017), age 70±7 yrs. Population was assessed for preoperative staging (30 pts, 65±9yrs, PSA median value 10), recurrence detection (158 pts, 71±7yrs, PSA median value 0.55 ng/ml), negative repeated biopsy (10 pts, 68±8yrs, PSA median value 6.6 ng/ml). Gleason Score (GS) was reported in 162 pts (tab.1).
Overall, 58 patients had positive scan results (93.1% with GS 7-9). In the staging group PSMA detected metastatic lesions in 5 pts (median PSA value 19 ng/ml) and lymphnode (LN) involvement in 2 pts confirmed after surgery. In the recurrence setting (158 pts, T3a in 73 pts, 9/158 N+, PSA doubling time 10.38±8 mo, PSA velocity 1.3±1.6 ng/ml/yr) PSMA-PET/CT revealed LN involvement in 28 pts (median PSA 0.52 ng/ml) and metastases in 23 pts (median PSA 0.6 ng/ml): in most of the pts metastases were in the bone (20 pts), 2 pts had lung and 1 liver metastases (biopsy proven). PSMA-PET/CT results changed treatment planning in all pts with metastatic disease despite the low levels of PSA and guided treatment plan in patients with isolated lesions (radiotherapy, surgery, local treatment).

==fine results==

==inizio discussions==

The detection of metastases at especially low PSA values is not reliable enough with the current guideline-recommended imaging modalities. There is growing interest in non-FDG molecular imaging agents that may have greater sensitivity and specificity and may potentially add phenotypic information for the tailoring of individualized salvage therapies.  In this context, PSMA-PET/CT has emerged as a promising, more accurate method.  The multidisciplinary context of the PCa Unit allows appropriate utilization of complex diagnostic tools as PSMA-PET/CT directly connecting disease assessment and treatment planning decisions.

==fine discussions==

==inizio conclusion==

In medium and high-risk pts PSMA-PET/CT is a useful tool to detect distant lesions and LN involvement (driving to sistemic or local treatment for confined lesions) even at very low PSA values. In the staging setting PSMA-PET/CT may support surgical decision expecially in pts with comorbidities. A positive PSMA-PET/CT changes treatment management in most of the patients expecially referring toward metastasis-directed therapies.

==fine conclusion==

==inizio reference==

1. Israeli RS, Powell CT, Fair WR, Heston WDW. Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 1993;53:227–230
2. Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: A study of 184 cases.Cancer.1998;82:2256–2261
3. Ross JS, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, Webb I, Gray GS, Mosher R, Kallakury BV. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003 Dec 15;9(17):6357-62. PubMed PMID: 14695135.
4. Bailey J, Piert M. Performance of (68)Ga-PSMA PET/CT for Prostate Cancer Management at Initial Staging and Time of Biochemical Recurrence. Curr Urol Rep. 2017 Sep 9;18(11):84. doi: 10.1007/s11934-017-0736-1. Review. PubMed PMID: 28889366
5. Lawrentschuk N. Sensitivity, Specificity, and Predictors of Positive(68)Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2016 Dec;70(6):926-937. doi: 10.1016/j.eururo.2016.06.021. Epub 2016 Jun 28. Review. PubMed PMID: 27363387.
6. Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New strategies in prostate cancer: Prostate-specific membrane antigen (PSMA) ligands for diagnosis and therapy. Clin. Cancer Res. 2016;22:9–15.
7. Eder M, Eisenhut M, Babich J, Haberkorn U. PSMA as a target for radiolabeled small molecules. Eur. J. Nucl. Med. Mol. Imaging. 2013;40:819–823
8. Silvia Migliari, Antonino Sammartano, Maura Scarlattei, Giulio Serreli, Caterina Ghetti, Carla Cidda, Giorgio Baldari, Ornella Ortenzia, and Livia Ruffini. Development and Validation of a High-Pressure Liquid Chromatography Method for the Determination of Chemical Purity and Radiochemical Purity of a [68Ga]-Labeled Glu-Urea-Lys(Ahx)- HBED-CC (Positron Emission Tomography) Tracer. ACS Omega 2017, 2, 7120-7126

==fine reference==