R. Jeffrey Karnes

MP77-17 IMPACT OF TIME FROM BIOPSY TO SURGERY ON COMPLICATIONS, FUNCTIONAL AND ONCOLOGIC OUTCOMES FOLLOWING RADICAL PROSTATECTOMY

on AS must undergo PSA testing and repeated biopsies over time in all proposed protocols and patients are subjected to discomfort and anxiety as well as to the complications of repeated biopsies. We tried to identify the predictors of progression-free survival (PFS) at a single institution AS program in order to identify patients in whom repeated biopsies could be avoided or reduced in frequency. METHODS: Between 2009 and 2016, 235 consecutive patients affected by low-risk PCa according to PRIAS criteria (cT1/T2a; PSA<10 ng/ml; PSA density <0.2; Gleason score <7; <3 positive cores) were enrolled in our AS program. Tumor progression was defined as pathological upgrading (Gleason >6 or >2 positive cores) at repeated yearly biopsies. First, Kaplan-Meier analyses were used to quantify progression-free survival at 1, 3 and 5 years, respectively. Second, we identified patients who were progression-free at 3 years of follow-up. Finally, univariable and multivariable logistic regression analyses were used to predict 3-year PFS. Covariates consisted of age, total PSA, clinical stage (cT) and number of positive cores at the time of enrolment as well as negative (no cancer) 1-year biopsy. RESULTS: Progression-free survival rate was 85%, 55%, and 40% at 1, 3 and 5 years, respectively. Median follow-up was 19 months. Overall, 56 (23.8%) patients were progression-free at 3 years of followup. Median number of cores at enrolment in AS program was 16 (IQR: 14-20), while median number of cores at first-year biopsy was 18 (IQR: 14-20). At univariable analyses, total PSA and negative 1-year biopsy were significant predictors of 3-year PFS (all p<0.05). Patients with negative biopsy at 1 year had a 3-year PFS of 75.8 vs. 29.0% in those with positive biopsy at 1-year. These results were confirmed at multivariable analyses, where a negative 1-year biopsy represented the only independent predictor of 3-year PFS (OR: 2.47; p1⁄40.04). CONCLUSIONS: The first biopsy after enrolment in AS program is an important predictor of PCa progression in the first 3 years in men on AS. Negative findings at 1-year biopsy suggest a high chance of 3-year PFS. Patients with negative 1-year biopsy could be followedup with less stringent biopsy protocol, in order to reduce possible biopsy-related side effects and discomfort.

MP53-16 LONG-TERM ONCOLOGIC OUTCOMES OF ADDING RADICAL PROSTATECTOMY TO CASTRATION FOR PATHOLOGICAL NODE-POSITIVE PROSTATE CANCER

any urinary leak) after RP and post IMRT was achieved in 29 (69%) and 27 (64.3%), respectively. After a median follow up of 3.4 years, a PSA recurrence and clinical recurrence were observed in 7 (16.7%) and 4 (9.5%) patients. A 5-year biochemical and clinical recurrencefree survival rate were 70.7% and 84.0%, respectively. 5-year overall free survival was 93.6%. None of patients died for prostate cancer during follow up. CONCLUSIONS: This phase II trial test a novel multimodal treatment paradigm for high-risk prostate cancer. Toxicity was acceptably low and long term oncological outcomes were good. Further studies are needed to compare this novel treatment paradigm to the standard of care.

PD72-07 MULTIPARAMETRIC MRI AFTER RADICAL PROSTATECTOMY PREDICTS SALVAGE RADIOTHERAPY OUTCOMES FOR PROSTATE CANCER

Nicola Fossati*, Milan, Italy; R. Jeffrey Karnes, Stephen Boorjian, Michele Colicchia, Rochester, NY; Alberto Bossi, Thomas Seisen, Villejuif, France; Cesare Cozzarini, Claudio Fiorino, Barbara Noris Chiorda, Giorgio Gandaglia, Milan, Italy; Thomas Wiegel, Ulm, Germany; Shahrokh F. Shariat, Gregor Goldner, Vienna, Austria; Steven Joniau, Antonino Battaglia, Karin Haustermans, Gert De Meerleer, Leuven, Belgium; Val erie Fonteyne, Piet Ost, Ghent, Belgium; Hein Van Poppel, Leuven, Belgium; Francesco Montorsi, Alberto Briganti, Milan, Italy

MP34-03 ONCOLOGIC OUTCOMES FOR PATIENTS WITH RESIDUAL CANCER AT CYSTECTOMY FOLLOWING PREOPERATIVE CHEMOTHERAPY: A PATHOLOGIC STAGE-MATCHED COMPARATIVE ANALYSIS

INTRODUCTION AND OBJECTIVES: While neoadjuvant chemotherapy prior to radical cystectomy (RC) has been demonstrated to improve survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after preoperative chemotherapy (POC) are less clear. As such, we evaluated survival for patients with and without rUCB at RC after POC compared with pathologic stage-matched RC patients who did not receive POC. METHODS: Patients undergoing RC for UCB between 19802010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received POC for T2-T4 and/or N1-3 M0 UCB were matched 1:2 to patients not exposed to prior chemotherapy based on pT and pN-stage, soft tissue surgical margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between POC and cancer-specific (CSS) and overall survival (OS), stratified by presence or absence of rUCB at RC. RESULTS: We matched 111 patients who underwent POC + RC to 222 RC-alone patients. Median age was 68 yrs (IQR 60,74); 59 (18%) were female. Median follow-up was 7.2 yrs (IQR 6,16), during which time a total of 248 patients died, with 148 dying from UCB. In patients without rUCB at RC, there was no difference in 5-yr CSS (86% vs. 90%, p1⁄40.85) or OS (82% vs. 84%, p1⁄40.46) between patients who did versus did not receive POC. Moreover, on multivariable analysis, chemotherapy exposure was not significantly associated with CSS (HR1⁄41.0; 95%CI 0.3-3.1; p1⁄40.9) or OS (HR1⁄40.9; 95%CI 0.4-1.9; p1⁄40.8) in this subgroup. Conversely, among patients with rUCB at RC, receipt of POC was associated with significantly worse 5-yr CSS (32% vs. 56%, p<0.001) and OS (25% vs. 48%, p<0.001). Moreover, on multivariable analysis, chemotherapy exposure remained independently associated with adverse CSS (HR1⁄42.2; 95%CI 1.6-3.1; p<0.001) and OS (HR1⁄42.0; 95%CI 1.5-2.7; p<0.001) among the patients with rUCB. CONCLUSIONS: While patients who achieve a complete response to POC have excellent survival outcomes, patients with residual UCB at RC after POC have a worse prognosis compared to stage-matched RC patients not exposed to chemotherapy. Such patients should be considered for enrollment in novel adjuvant therapy trials, while continued investigation of which patients are most likely to achieve ypT0 status remains warranted.

MP93-16 IMPACT OF OBESITY ON PROSTATE CANCER RECURRENCE AFTER RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: When operating deep in the abdomen and pelvis, excess fat can interfere with accessing key anatomical structures and create difficulty in dissection and reconstruction. Since intraperitoneal fat is avoided during extraperitoneal robot assisted radical prostatectomy (eRARP), some Urologists have advocated this approach over its transperitoneal counterpart (tRARP) when operating on morbidly obese men (BMI>40). Herein, we aim to compare outcomes of eRARP vs. tRARP in the morbidly obese. METHODS: A chart review of patients who have undergone robot assisted radical prostatectomy (RARP) at a tertiary care academic center from July 1, 2003 through April 30, 2016 was undertaken. Patients with BMI >40 were identified. Those with concomitant inguinal hernia repair were excluded. The resulting eRARP and tRARP groups were compared for demographic, clinical and pathologic characteristics. Regression analysis was performed between the groups with Age, BMI, ASA score and D’Amico classification as selected covariates. RESULTS: 3168 patients underwent RARP during this time period, of which 82 patients met our inclusion and exclusion criteria; each group comprised 41 patients. No differences were noted in age, BMI, ASA score or pre-operative PSA. The tRARP group had a higher clinical stage (p1⁄40.016), biopsy Gleason score (p1⁄40.007) and D’Amico risk category (p<0.00001). The tRARP group had a higher rate of pelvic lymph node dissection (PLND, p<0.00001). No differences were noted in rate of nerve sparing. No differences were noted in OR time, estimated blood loss (EBL), length of stay (LOS) or time to catheter removal (TCR). No differences were noted in surgical margin status or overall complications (either calculated as binary or total number). On regression analysis, no differences were noted in complications, OR time, LOS, TCR or EBL. CONCLUSIONS: In this cohort, surgical approach (eRARP vs. tRARP) did not affect intraor peri-operative outcomes in morbidly obese men undergoing RARP so surgeons should tailor their approach based on comfort level.

PD71-03 NOVEL DNA METHYLATION MARKERS FOR ACCURATE PROGNOSTIC ASSESSMENT OF PROSTATE CANCER: DISCOVERY AND EARLY VALIDATION

INTRODUCTION AND OBJECTIVES: The prostate health index (PHI) is superior to PSA and other PSA-derivatives for the detection of prostate cancer (PCa). We sought to explore the utility of PHI density for the detection of clinically-significant PCa in a contemporary cohort of men presenting for diagnostic workup of PCa. METHODS: The study cohort includedpatientswith elevatedPSA (>2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serummarkers were prospectively measured per standard clinical pathway. PHI was calculated as [([-2]proPSA/free PSA) x (PSA)], and density calculations were performed using prostate volume as determined on transrectal ultrasound. Logistic regression was used to assess the ability of serum markers to predict clinically-significant PCa, defined as any Gleason score 7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core. RESULTS: Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically-significant PCa on biopsy. The median PHI density was 0.70 (IQR 0.43-1.21); it was 0.53 (IQR 0.360.75) in men with negative biopsy or clinically-insignificant PCa and 1.21 (IQR 0.74-1.88) in men with clinically-significant PCa (p<0.001). Clinically-significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the interquartile range (0.43-1.21) of PHI density, and 80.0% of men with PHI density >1.21 (p<0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically-significant PCa, and 100% sensitive for Gleason score 7 disease. Compared to PSA (AUC 0.52), PSAD (AUC 0.70), % free PSA (AUC 0.75), and PHI (AUC 0.76), PHI density demonstrated the highest discriminative ability for clinically-significant PCa (AUC 0.84). CONCLUSIONS: Based on this prospective single-center experience, PHI density could be used to avoid 38% of unnecessary biopsies while failing to detect only 2% of clinically-significant cancers.

MP20-01 VALIDATION OF THE AMERICAN JOIN COMMITTEE ON CANCER (AJCC) 8TH EDITION PROSTATE CANCER STAGING SYSTEM

INTRODUCTION AND OBJECTIVES: In the recently published 8 edition update of the AJCC staging system for prostate cancer (PCa), pT2a/b/c sub-classifications were consolidated as pT2. Also, serum prostate-specific antigen (PSA) 20ng/ml or Grade Group (GG) 5 now classify patients as Stage III disease. We sought to validate these changes in a large institutional registry with long-term follow-up. METHODS: Men who underwent radical prostatectomy without prior therapy at Mayo Clinic between 1987-2011 were identified. The prognostic significance of a single pT2 designation was compared to previous stratification as unilateral (pT2a-b) versus bilateral (pT2c). Further, 7 edition Stage II patients were then re-categorized based on the presence or absence of PSA 20ng/ml and GG 5. Biochemical recurrence-free (BCR) survival, systemic progression-free survival (sPFS), and cancer-specific survival (CSS) were evaluated using Kaplan Meier analyses and multivariable Cox regression models, adjusting for age, Gleason score, preoperative PSA, and surgical margin status. RESULTS: The overall cohort included 17,846 men with a median follow-up of 11 years (IQR 7,16), during which time 5021 experienced BCR, 1246 progressed systemically, and 641 died from PCa. Among pT2 patients, sub-stratification was not independently associated with BCR-free survival (HR1⁄41.0; 95%CI 0.9-1.1; p1⁄40.69), sPFS (HR1⁄41.0; 95%CI 0.8-1.3; p1⁄40.68), or CSS (HR1⁄40.9; 95%CI 0.61.2; p1⁄40.41). Meanwhile, patients previously classified with Stage II disease who had a preoperative PSA 20ng/ml (now Stage III) had a 15-year CSS that was significantly worse than Stage group II patients with PSA < 20ng/ml (88% vs 94%; p<0.001), but similar to 7 edition Stage III patients (88% vs 86%; p1⁄40.12). On the other hand, Stage II patients now classified as Stage III based on GG 5 had a 15 year CSS that was significantly worse than both 7 edition Stage II patients with GG 1-4 (48% vs 68%; p<0.001) and 7 edition Stage III patients (48% vs 60%; p<0.001). Results for BCR-free survival and sPFS were similar. CONCLUSIONS: We validate the new AJCC pT2 staging classification. Moreover, our data support the designation of patients with a PSA 20ng/ml as Stage III disease. Interestingly, while upstaging GG5 patients from Stage II to III is an improvement, these patients have even worse outcomes than 7 edition Stage III patients, emphasizing the particular prognostic significance of the new GG and the importance of including GG in staging classification.

MP77-04 IMPLICATIONS OF RECURRENCE SITES IDENTIFICATION FOLLOWING SALVAGE TREATMENTS FOR PROSTATE CANCER USING C-11 CHOLINE PET AND MULTIPARAMETRIC MRI

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.