Luisa Pasini

Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: Results from a prospective single-center study.

BACKGROUND The aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP). METHODS The study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen ≥0.2 ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index. RESULTS Mean total prostate-specific antigen and mean PHI levels were 5.76 ng/ml (interquartile range: 4.2-8.7) and 46.0 (35-62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and ≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level ≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were. CONCLUSIONS Preoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed.

Active surveillance for low-risk non-muscle-invasive bladder cancer: Mid-term results from the Bladder cancer Italian Active Surveillance (BIAS) project.

To report the oncological safety and the risk of progression for patients with non‐muscle‐invasive bladder cancer (NMIBC) included in an active surveillance (AS) programme after the diagnosis of recurrence.

Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project

Purpose: We investigated predictive factors of failure and performed a resource consumption analysis in patients who underwent active surveillance for nonmuscle invasive bladder cancer. Materials and Methods: This prospective observational study monitored patients with a history of pathologically confirmed stage pTa (grade 1‐2) or pT1a (grade 2) nonmuscle invasive bladder cancer, and recurrent small size and number of tumors without hematuria and positive urine cytology. The primary end point was the failure rate of active surveillance. Assessment of failure predictive variables and per year direct hospital resource consumption analysis were secondary outcomes. Descriptive statistical analysis and Cox regression with univariable and multivariable analysis were done. Results: Of 625 patients with nonmuscle invasive bladder cancer 122 with a total of 146 active surveillance events were included in the protocol. Of the events 59 (40.4%) were deemed to require treatment after entering active surveillance. Median time on active surveillance was 11 months (IQR 5–26). Currently 76 patients (62.3%) remain under observation. On univariable analysis only time from the first transurethral resection to the start of active surveillance seemed to be inversely associated with recurrence‐free survival (HR 0.99, 95% CI 0.98–1.00, p = 0.027). Multivariable analysis also revealed an association with age at active surveillance start (HR 0.97, 95% CI 0.94–1.00, p = 0.031) and the size of the lesion at the first transurethral resection (HR 1.55, 95% CI 1.06–2.27, p = 0.025). The average specific annual resource consumption savings for each avoided transurethral bladder tumor resection was &U20AC;1,378 for each intervention avoided. Conclusions: Active surveillance might be a reasonable clinical and cost‐effective strategy in patients who present with small, low grade pTa/pT1a recurrent papillary bladder tumors.

Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence

Although the pathophysiology of acute chronic cystitis and other ‘sensory’ disorders, i.e. painful bladder syndrome (PBS) or interstitial cystitis (IC), often remains multifactorial, there is a wide consensus that such clinical conditions may arise from a primary defective urothelium lining or from damaged glycosaminoglycans (GAGs). A ‘cascade’ of events starting from GAG injury, which fails to heal, may lead to chronic bladder epithelial damage and neurogenic inflammation. To restore the GAG layer is becoming the main aim of new therapies for the treatment of chronic cystitis and PBS/IC. Preliminary experiences with GAG replenishment for different pathological conditions involving the lower urinary tract have been reported. There is a range of commercially available intravesical formulations of these components, alone or in combination. Literature evidence shows that exogenous intravesical hyaluronic acid markedly reduces recurrences of urinary tract infections (UTIs). Patients treated with exogenous GAGs have fewer UTI recurrences, a longer time to recurrence and a greater improvement in quality of life. Exogenous intravesical GAGs have been used for the treatment of PBS/IC. Despite the limitations of most of the studies, findings confirmed the role of combination therapy with hyaluronic acid and chondroitin sulfate as a safe and effective option for the treatment of PBS/IC. To prevent and/or treat radiotherapy and chemotherapy induced cystitis, GAG replenishment therapy has been used showing preliminary encouraging results. The safety profile of exogenous GAGs has been reported to be very favourable, without adverse events of particular significance.

Feasibility and Clinical Roles of Different Substaging Systems at First and Second Transurethral Resection in Patients with T1 High-Grade Bladder Cancer

BACKGROUND Decision making in T1 high-grade bladder cancer patients remains a challenging issue in urologic practice. OBJECTIVE To assess the feasibility and potential prognostic role of three different substaging systems in specimens from both primary and second transurethral resection (TUR) of the bladder in T1 high-grade bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS A total of 250 consecutive, confirmed pure transitional T1 high-grade bladder tumors submitted to second TUR entered the retrospective study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Feasibility of two already clinically tested microstaging systems (anatomy-based T1a/T1b/T1c and micrometric T1m/T1e with 0.5-mm thresholds of invasion) and that of a micrometric substage designed by the authors and based on a 1-mm threshold of invasion (Rete Oncologica Lombarda [ROL] system) was assessed by five independent uropathologists on both first and second TUR specimens. Univariable Cox proportional hazards models were attempted to identify significant independent predictors of recurrence and progression after TUR. Kaplan-Meier curves were plotted to compare different substaging methods analyzing recurrence and progression. RESULTS AND LIMITATIONS The ROL system proved to be feasible in nearly all cases at both first and second TUR. Median follow-up was 60 mo. The univariate Cox regression analysis documented the ROL substage (ROL2 vs ROL1) to be the only statistically significant predictor of progression (hazard ratio: 2.01; 95% CI, 1.03-3.79; p<0.03). For the first time to our knowledge, the substage was investigated and used to assess T1 tumors found at second TUR, registering a high rate of feasibility. CONCLUSIONS T1 microstaging using different procedures is feasible on both primary- and second-TUR specimens. A high rate of feasibility may be expected for T1m/T1e and ROL systems. The clinical role of microstaging on second TUR remains to be defined. PATIENT SUMMARY The Rete Oncologica Lombarda system showed feasible results in T1 high-grade bladder tumors. Our substratification was predictive of progression of disease.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study

Purpose: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. Materials and Methods: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging‐Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). Results: A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum‐to‐background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum‐to‐background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum‐to‐background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. Conclusions: Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

MP64-07 VASCULAR HURST INDEX IN NON-TUMORAL BIOPSY CORES AS POTENTIAL HISTOPATHOLOGICAL PARAMETER TO SELECT PATIENTS WITH HIDDEN PROSTATE CANCER

METHODS: 44 cases were analyzed that are surgically operated with robot-assisted radical prostatectomy performed from February to September in 2016. Preoperative MRI have been conducted for all 44 cases, and the prostate cancer local diagnoses (Region of Interest: ROI) were determined by radiologists using MRI T2 weighed image and Diffusion Weighed Image (DWI), then finally the scores of ADC were calculated. IHC for aSMA, vimentin, CD105, and Tenascin-C (TNC-C) were conducted and classified into three group (none stained, weakly stained, strongly stained) to check the relation of those IHC findings to MRI ADC score before the treatment. RESULTS: The average of minimum ADC scores in ROC of these prostate cancer patients before surgery was 0.779 (SD1⁄40.173). IHC comparison were made according to the cut off value of the minimum ADC scores between more (n1⁄418, group A) and less (n1⁄426, group B) than 0.800. 66% (12/18) patients showed strongly stained findings for aSMA in group A. Meanwhile, vimentin, CD105, and TNC-C showed strong stained in B group, 22.2% (4/18) and 61.5% (16/26), 22.2% (4/18) and 0% (0/26), and, 33.3% (6/18) and 76.9% (20/26) in group A and B, respectively.(Conclusions) CONCLUSIONS: To use these multi-parametric MRI findings, especially pretreatment ADC scores, our results suggested postoperative IHC findings and more to address, tumor microenvironment could be predicted.Themorevarious treatmentselectionhavebeenandcouldbeapplied to prostate cancer, such as upfront chemotherapy and wide resection for surrounding tissues, themorepreciseprocedureareneeded topredict tumor microenvironment in order to detect potentially aggressive prostate cancer.

MP64-17 EXTRACELLULAR COLLAGENIC TYPE AND STRUCTURAL ORGANIZATION CHANGES IN PROSTATE CANCER AND BENIGN PROSTATIC HYPERPLASIA

Fabio Grizzi*, Rozzano (MI), Italy; Alberto Mandressi, Castellanza (VA), Italy; Piergiuseppe Colombo, Rozzano (MI), Italy; Sara Melegari, Matteo Justich, Giorgio Bozzini, Mauro Seveso, Oliviero De Francesco, Castellanza (VA), Italy; Nicol o Buffi, Giovanni Lughezzani, Massimo Lazzeri, Rodolfo Hurle, Luisa Pasini, Alessio Benetti, Silvia Zandegiacomo, Roberto Peschechera, Paolo Casale, Giorgio F. Guazzoni, Rozzano (MI), Italy; Gianluigi Taverna, Castellanza (VA), Italy

MP03-18 ABSENCE OF LEARNING CURVE IMPACT MAY LET MRI-TRUS FUSION GUIDED BIOPSY UP FOR EARLY DIAGNOSIS OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: To evaluate the impact of urologist learning curve (LC) for mpMRI-TRUS fusion biopsy on clinically significant PCa (sPCa) detection rate. METHODS: Data from 291 patients who underwent mpMRITRUS transperineal/transrectal targeted (TB) and systematic transrectal biopsy (SB) for suspicion of PCa were prospectly collected at a single institution. For mpMRI-TRUS fusion-guided prostate biopsy, the BioJet fusion system (D&K Technologies, Germany) was used; biopsies were performed in a transrectal or transperineal setting according to the location of the primary lesion on the mpMRI. All the procedures were performed by two urologists who had already experience with TRUS guided random prostate biopsies. mpMRI studies were reported by different experienced radiologists. The cohort was divided into six groups representing consecutive times during the study period. Overall PCa detection rate (CDR) and csPCa detection rate (csCDR), defined with Epstein criteria, were reported and stratified according to progression groups. Sensitivity, specificity, negative predictive value and accuracy of MRI-TRUS TB were calculated. Linear regression analyses were performed to evaluate the learning curve of the procedure. RESULTS: Overall PCa detection rate was 42.6% (n1⁄4124) and csPCa detection rate was 28% (n1⁄481). CDR at target biopsy was 38% (n1⁄4111). Considering CDR stratified according to PIRADS, we reported 16.7% (n1⁄41), 21% (n1⁄422), 50.7% (n1⁄474) and 75% (n1⁄427) for PIRADS 2, 3, 4 and 5 respectively(p<0.01). Cancer detection rate increased from 38.8% to 42.6% from group A to group F (R21⁄40.06). csCDR and target biopsy CDR increased from 22% to 42% (R21⁄40.002) and from 38.8% to 39.5% (R21⁄40.7) respectively. Sensitivity, specificity, NPV and accuracy of TB in detecting PCa was 79% (CI: 0.68-0.89), 73% (CI: 0.66-0.78), 93 % (0.89-0.96) and 74% (0.680.79) respectively. Sensitivity, specificity, NPV and overall accuracy of TB in detecting csPCa was 93% (CI: 0.86-0.98), 83% (CI :0.77-0.87), 96% (CI:0.94-0.99) and 85% (CI: 0.81-0.89) respectively. When the LC impact was assessed, overall diagnostic accuracy on PCa and csPCa of TB did not show a significant increasing trend (R21⁄40.5 and R21⁄40.09). CONCLUSIONS: We failed to demonstrate a statistically significant impact of LC for PCa and csPCa detection. mpMRI-TRUS-TB seems to be an easy, reliable and feasible procedure in the hands of experienced urologists. Our findings represent a starting point for faster widespread of the technique in the urological practice.

MP77-03 TARGETED 11C-CHOLINE PET/CT/TRUS SOFTWARE FUSION-GUIDED PROSTATE BIOPSY HAS IN MEN WITH PERSISTENTLY ELEVATED PSA AFTER PREVIOUS NEGATIVE BIOPSY

INTRODUCTION AND OBJECTIVES: Assess the feasibility and the accuracy of targeted prostate biopsy with standard (systematic 12-core) biopsies after fusion imaging of choline-PET/CT (choline-PET) and multiparametric MRI (mpMRI) with 3D-transrectal ultrasound (TRUS) to detect prostate cancer. The Fusion of the two modality with echography 3d was try to compare the diagnostic performance for localization of primary PCa with (mpMRI) and last generation of PET/CT (Biograph mCT Flow, Siemens). METHODS: Within a prospective single-center study, from December 2014 to October 2016, 31 patients with a rising PSA ? 10ng/ ml or with an history of a negative prostate biopsies were included, and performed a choline-PET and a mpMRI. PET and T2-weighted MR volumes of the prostate were spatially registered using commercially available software. Biopsy targets were selected on both modalities. TRUS biopsy using the real-time 3D TRUS-tracking system (Urostation Touch , Koelis, France), which enabled US-guided and/or MR/US fusion targeted biopsies. The biopsy procedure was performed after registration of real-time TRUS with mpMRI and choline-PET by the same operator, using 3D TRUS-tracking system. At the time of biopsy, volume data of the mpMRI and PET 18-ch was elastically fused with TRUS. Each target was biopsied twice. Histologic results were determined from standard and targeted biopsy cores. RESULTS: Mean PSA was 13.01 ng/ml (5.32-73). Mean number of biopsy was 16 (13-21) and mean prostate volume was 63.41 cc (25-169). The cancer detection rate was 69%. The cancer detection rate with standard biopsies off target was 42% and with prostate targeted biopsy was 50% using PET, 65% using mpMRI with a sensibility of 72%, 94%, 100% respectively for PET, mpMRI or both . The average number of positive cores was respectively 1.77 (1-7) ,2.74 (3-11) for PET and mpMRI. CONCLUSIONS: We demonstrated the feasibility and accuracy of multimodal image registration for targeted prostate biopsies with echography 3D to define localization of prostate cancer, compared to standard biopsies. It was very interesting to observe sometimes a great difference in the distribution of PET choline targets and mpMRI targets in the prostate. mpMRI was probably better than PET to detected prostate cancer but it could be complementary. A new study with a novel ligands targeting prostate specific membrane antigen (PSMA) could improve our clinical results.