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METHODS: We studied pathological outcomes in men who underwent RP after some time on AS. All men met the original Epstein criteria (clinical stage T1, PSA density < 0.15, biopsy Gleason score 6, 2 positive biopsy cores, 50% involvement of any core) at the time of diagnosis. We identified men who reclassified by the original Epstein criteria, or by the modified Epstein criteria (clinical stage T1, PSA density < 0.15, biopsy Gleason score 6, 2 positive biopsy cores, unilateral tumor). Pathological outcomes were compared between men with and without evidence of disease reclassification on AS, and factors associated with adverse pathology (defined as pathological stagepT3a, RP Gleason 4+3, or lymph node involvement) were determined. RESULTS: Of 1086 men enrolled in AS, 130 (12%) men who met the Epstein criteria at the time of diagnosis underwent RP after a median time of 1.96 years on AS. 97 (75%) of these men reclassified by the original Epstein criteria while on AS. 95 of the 130 men met the modified Epstein criteria at diagnosis, and 85 (90%) men were reclassified by these criteria. Using the original criteria, rates of adverse pathology were greater in men with evidence of reclassification compared to those without (p¼0.05). On multivariable analysis, reclassification by PSA density (p¼0.05) and biopsy Gleason score (p¼0.03) were associated with adverse pathology, whereas reclassification by number of positive biopsy cores (p¼0.78) and percent core positivity (p¼0.51) were not. Longer time on AS was likewise not associated with adverse pathology (p¼0.68). CONCLUSIONS: Adverse pathology after RP is more common in men with evidence of disease reclassification on AS compared to those undergoing RP for other reasons. However, we identified varying outcomes among these patients depending on the criterion that defined reclassification. These data may enable identification of men who can safely continue on AS despite evidence of disease reclassification.
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tGS, the qGS remained significantly associated with BCR (P<0.01), whereas the tGS was not (p¼0.78). CONCLUSIONS: The qGS is a simple modification of the Gleason grading system, based on the weighted average of Gleason patterns present in the pathology specimen. This external validation confirms the ability of the qGS to predict BCR after RP with greater precision than the tGS. The qGS may help to identify men at high risk of recurrence who may benefit from adjuvant therapy after RP.
Source of Funding: Supported in part by The Warburton Family Foundation and Dr. Hugh Judge Jewett Fellowship in Urologic Oncology
MP51-13 EXTERNAL VALIDATION OF THE QUANTITATIVE GLEASON SCORE IN PREDICTING PROSTATE CANCER RECURRENCE AFTER RADICAL PROSTATECTOMY Adam Reese*, Philadelphia, PA; Elen Woldemichael, Pittsburgh, PA; Matthew Cooperberg, San Francisco, CA; Joel Nelson, Pittsburgh, PA INTRODUCTION AND OBJECTIVES: The quantitative Gleason score (qGS) is a modification of the current Gleason grading system for prostate cancer, based on the weighted average of high vs. low grade tumor in a pathology specimen. The qGS aims to capture the continuum of risk associated with higher volumes of poorly differentiated disease. The value of the qGS in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) has been previously reported in a single institution series. This study aims to validate the predictive ability of the qGS in an external dataset. METHODS: We identified patients who underwent RP at the University of Pittsburgh Medical Center between 1999 and the present, and were found to have a traditional Gleason score (tGS) of 3+4 or 4+3 on final pathology. The qGS was calculated in these men according to the following equation: qGS ¼ 2 x [(3 x %Gleason pattern 3) + (4 x %Gleason pattern 4)] Time to BCR after RP was determined. Using Kaplan-Meier (KM) and Cox proportional hazards regression, we compared the ability of qGS vs. tGS to predict BCR after RP. RESULTS: 1277 men met the study inclusion criteria. Using the tGS, 1034 (81%) were pathological Gleason 3+4 and 243 (19%) were Gleason 4+3. Over a median of 56 months, 133 (10%) patients developed BCR. In KM analysis, the qGS allowed for a finer assessment of BCR risk compared to the tGS (see figures 1&2). In multivariable analysis the qGS was significantly associated with BCR (HR 5.24, 95% CI 3.49-7.87). The c-index for the qGS model exceeded that of the tGS model (0.85 vs. 0.83). In a model incorporating both the qGS and the
Source of Funding: Partially supported by The Warburton Family Foundation and Dr. Hugh Judge Jewett Fellowship in Urologic Oncology
MP51-14 A COMPARISON OF 111IN-J591 SPECT WITH 89ZR-J591 PET IMAGING FOR PROSTATE CANCER PATIENTS. Sandhya Chalasani*, Shoaib Fareedy, Sarah Lindgren-Belal, Daniel Spratt, Brian Robinson, Joseph Osborne, Neil Bander, Douglas Scherr, New York, NY INTRODUCTION AND OBJECTIVES: To compare pilot cohorts of men scheduled for radical prostatectomy imaged with novel antibody conjugates: Cohort 1 (111In-J591) single photon emission tomography (SPECT) or Cohort 2 (89Zr-J591) positron emission tomorgraphy (PET). METHODS: 1) Cohort 1: Eight patients with abnormal digital rectal exam and biopsy proven prostate cancer were injected intravenously with two milligrams of J591 labeled with 5mCi of 111In. SPECT/ CT imaging was performed 2 to 5 days post injection. Prostatectomy
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was performed on the day of imaging and the excised prostate was imaged with SPECT/CT and planar scintigraphy before being sent to surgical pathology. 2) Cohort 2: Eleven patients were injected intravenously with 5mCi 89Zr-J591 followed 6 days later by whole body PET imaging. Patients underwent surgery the day of PET imaging and the specimens were imaged by ex vivo PET and custom 3 Tesla magnetic resonance scanner coil. SPECT/ PET imaging studies and histopathology were correlated. RESULTS: 111In-J591 whole body images showed the expected bio-distribution seen in other ongoing imaging/therapy trials for metastatic Prostate Cancer (PCa). Imuno-scintigraphic images were consistent with the pathologic diagnoses for all of the patients. In case of 89Zr-J591/PSMA PET imaging in localized PCa it is observed 89ZrJ591-PET binds to tumor foci in situ and binds primarily to Gleason 7 and larger sized tumors, likely corresponding to clinically significant disease that warrants definitive therapy. CONCLUSIONS: 111In-J591 demonstrated targeting in localized disease in prostatectomy specimen, but pathologic validation was only inferred by quadrant due to low soft tissue contrast and the inherent resolution limits of the clinical scanner on a relatively small specimen. 89Zr-J591-PET can identify discrete intra-prostatic tumor foci, and in our cohort, visualized most of the index lesions. Additionally, high-grade tumors are generally better visualized with this novel imaging agent. There is a relationship between SUV on the 89Zr-J591-PET of tumor foci and their aggressiveness as defined by Gleason score. The preliminary data from this pilot study warrants further investigation with MicroSPECT and autoradiograph or ImmunoPET and MRI. Source of Funding: None
MP51-15 TIME FROM SURGERY TO URINARY CONTINENCE SIGNIFICANTLY INFLUENCES THE SUBSEQUENT RECOVERY OF ERECTILE FUNCTION IN PATIENTS TREATED WITH BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY Giorgio Gandaglia*, Firas Abdollah, Andrea Gallina, Paolo Dell’Oglio, Maria Passoni, Andrea Salonia, Vincenzo Scattoni, Niccolo Nicola Fossati, Damiano Vizziello, Milan, Italy; Pierre I. Karakiewicz, Maxine Sun, Montreal, Canada; Shahrokh F. Shariat, Vienna, Austria; Francesco Montorsi, Alberto Briganti, Milan, Italy INTRODUCTION AND OBJECTIVES: Time from surgery to patient evaluation represents an important predictor of subsequent erectile function (EF) recovery in prostate cancer (PCa) patients after nerve-sparing radical prostatectomy (NSRP). However, evidence is scarce regarding the role of time between urinary continence (UC) recovery on subsequent EF recovery after surgery. We hypothesized that the early UC recovery might be a reliable predictor of EF recovery after bilateral NSRP (BNSRP). METHODS: The study included 870 patients with PCa treated with BNSRP between January 2008 and July 2013 at a single institution. UC recovery was defined as being completely pad-free over a 24hour period. The International Index of Erectile Function-Erectile Function Index (IIEF-EF) was used to evaluate EF after BNSRP. Postoperative EF recovery was defined as an IIEF-EF domain score 22. We focused our analyses on preoperatively fully potent patients (namely, IIEF-EF26; n¼223). Cumulative survival estimates were used to generate conditional recovery rates assessed at 6-month intervals. Our analyses were repeated after stratifying patients according to age at surgery (65 vs. 66-70 vs. 71), CCI (0 vs. 1 vs. 2), and D’Amico risk group (low- vs. intermediate/high-risk). Multivariate Cox regression analyses (MVA) tested the relationship between early UC recovery (within 1 month after surgery) and EF recovery after adjusting for age at surgery, Charlson Comorbidity Index (CCI), and risk group. RESULTS: At a mean follow up of 43 months (median 40), the 1- and 2-year EF recovery rates were 54.9% and 64.5%, respectively. The 1- and 2-year UC recovery rates were 79.4 and 85.9%, respectively. In patients who were still incontinent at 1-, 6-, 12-, and 18-months
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after surgery, EF recovery rates in the following 6-month period substantially decreased as the time following surgery increased: 34.2, 31.6, 26, and 6.7%, respectively. Similar trends were observed after stratifying patients according to age at surgery, CCI, and risk group. In MVA, earlier UC was associated with 2-fold higher probability of EF recovery, after adjusting for confounders (P<0.001). CONCLUSIONS: The time elapsed between BNSRP and UC recovery has a substantial impact on the subsequent probability of EF recovery. Since UC recovery precedes EF recovery in the vast majority of the cases, these observations might help provide clinicians better postoperative counseling and planning of therapeutic approaches aimed at the optimal recovery of EF. Source of Funding: None
MP51-16 PATHOLOGIC FINDINGS AT RADICAL PROSTATECTOMY OF PATIENT’S ELIGIBLE FOR ACTIVE SURVEILLANCE: STRATIFICATION BY SELECTION CRITERIA AND RACE Kenneth DeLay*, Michael Williams, Norfolk, VA; Hind Beydoun, Norfolk, WA; Robert Given, Raymond Lance, Norfolk, VA INTRODUCTION AND OBJECTIVES: To compare prostate cancer specific outcomes between selection criteria for patients considering active surveillance(AS). METHODS: Materials & Methods: We queried our institutional radical prostatectomy (RP) database for pathologic data on prostatectomy specimens from 1991 to 2012. From this three groups were formed. Ultra low risk patients were defined as those with a Gleason 3+3 disease, no more than 30% tumor of involvement of one core, PSA <10, and cT2a or less on initial biopsy. Low risk was defined as Gleason 3+3 disease, 1-3 cores involved, no core with more than 50% tumor involvement, PSA <10, and cT2a or less. Intermediate risk was defined as those with Gleason 3+4 disease, one core involved, and no core with more than 30% involvement RESULTS: We identified 545 men from 3097 specimens who met eligibility the above criteria. The average age in years and PSA were 59.1 and 5.1 respectively. There were 414 Caucasians and 156 African-Americans. 23 patients did not have their race identified in the database. On multivariate analysis including age, race, and gland size no differences were found among groups with respect to pathologic stage, Seminal Vesicle Invasion, or biochemical recurrence. The intermediate risk groups did carry an increased risk of harboring primary Gleason 4 or 5 on final pathology compared to the low risk and ultra-low groups with Odds Ratios of 5.32 (2.24-12.65) and 10.92 (3.54-33.69). The low risk group did not have an increased risk of primary Gleason 4 or 5 compared to the ultra-low risk group. CONCLUSIONS: Patients with even low volume 3+4 disease adenocarcinoma of the prostate on initial biopsy are more likely to harbor Gleason 4 or 5 disease at final pathology compared to those with only low volume Gleason 3+3. However, in our cohort we did not see any other significant differences in other pathological findings nor and most importantly in biochemical disease free survival. Table Pathology Total Patients Extraprostatic Disease(T3) Semival Vesicle Invasion Positive Margins Biochemical Recurrence Primary Gleason 4/5 on Final Pathology
Ultra Low Risk 194 8.2%(16) 0.4%(1)
Low Risk 302 10.2%(31) 1.6(5)
Intermediate Risk 49 12.2%(6)
P value 0.75
4.2%(2)
0.41
18.6(40) 14.2%(31)
15.8%(50) 14.4%(47)
18.2%(11) 18.3%(9)
0.66 0.47
2.2%(5)
4.6%(15)
20.4%(10)
0.0001
Source of Funding: None