Maria Komisarenko

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup

PURPOSE We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. MATERIALS AND METHODS A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. RESULTS A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). CONCLUSIONS While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Is Routine Renal Tumor Biopsy Associated with Lower Rates of Benign Histology following Nephrectomy for Small Renal Masses

Purpose: Renal tumor biopsies have been proposed as a management alternative to avoid treatment of benign or low risk small renal masses. However, many urologists are reluctant to recommend renal tumor biopsy because they feel its result frequently will not impact management. Our primary objective was to evaluate if centers that routinely favor renal tumor biopsy have lower rates of benign histology after surgery than centers where a selective renal tumor biopsy approach is used. Materials and Methods: This was a retrospective multicenter study of patients who underwent partial or radical nephrectomy for a lesion suspicious for localized renal cell carcinoma which measured 4 cm or less (cT1a and pT1a or pT3a) between 2013 and 2015. A logistic regression model was used to examine whether the odds of obtaining a benign tumor following surgery differed between centers that routinely favor renal tumor biopsy and centers where a selective renal tumor biopsy approach is used. Results: A total of 542 small renal masses in 516 patients were included in study. The rate of histologically benign tumors after surgery was 11%. This rate was significantly lower at centers that routinely favor renal tumor biopsy than at centers where a selective renal tumor biopsy approach is used (5% vs 16%, p <0.001). On multivariable analysis older age, smaller tumors and centers where a selective renal tumor biopsy approach is used were significantly associated with greater odds of finding a histologically benign tumor postoperatively. Compared to centers that routinely favor renal tumor biopsy the odds of finding a benign tumor at surgery was 4 times more likely at centers where a selective renal tumor biopsy approach is used (OR 4.1, 95% CI 1.9–8.3). Conclusions: Routine renal tumor biopsy reduces surgery for benign tumors and the potential for short‐term and long‐term morbidity associated with these procedures. This study suggests that routine renal tumor biopsy may be a valuable tool to decrease overtreatment of small renal masses.

Active surveillance review: contemporary selection criteria, follow-up, compliance and outcomes

The primary goal of active surveillance (AS) is to prevent overtreatment by selecting patients with low-risk prostate cancer (PCa) and closely monitoring them so that definitive treatment can be offered when needed. With the increasing popularity of AS as a management strategy for men with localized PCa, it is important to understand all the contemporary guidelines and criteria that exist for AS and the differences among them. No single optimal management strategy for clinically localized, early-stage disease has been universally accepted. The implementation of AS varies widely between institutions, from inclusion criteria to follow-up protocols, with the most notable differences seen in maximum accepted Gleason score, T-stage and prostate-specific antigen (PSA) parameters. The objectives of this review were to systematically summarize the current literature on AS strategy, present an overview of the various published guidelines and criteria that are used for AS at several major institutions as well as discuss goals and trade-offs of the various criteria. A comprehensive search of the PubMed and Embase databases from 1990 to 2017 was performed to identify studies pertaining to AS criteria and trends. Trends in AS uptake and use in Canada, USA and Europe were reviewed to demonstrate the current trends and outcomes of AS to offer greater insight into the differences, nature and efficacy of various AS protocols. AS is a compelling antidote to the current PCa overtreatment phenomena; however, when considering patients for AS it is important to understand the differences between protocols, and review published results to appreciate the impact on follow-up.

MP67-20 IDENTIFYING BARRIERS TO THE ADOPTION OF PERCUTANEOUS RENAL TUMOUR BIOPSY IN THE MANAGEMENT OF SMALL RENAL MASSES

its low nuclear grade and minimal tumor burden. The present study aimed to characterize the clinical and pathologic features of MCRCC. METHODS: From January 2006 to December 2014, 76 cases were identified as MCRCC among 4345 patients with RCC at our institution. Their clinical and characteristics, surgical management, pathologic features, and outcomes were retrospectively reviewed. RESULTS: The incidence of MCRCC in our patients with RCC was 1.7%. The mean age at diagnosis was 46.7 10.5 years (range,18 to 80years).Most cases showednosymptoms.Nuclear gradewasunrelated to the TNM stage (P1⁄40.451). Of these 76 patients, 66 (86.8%) were followedup foramedianof52months, andno tumor recurrenceormetastasis was found, no differences were found in the prognosis of different TNM groups. CONCLUSIONS: The incidence of MCRCC in patients with RCC is low. The nuclear grade and prognosis of MCRCC cases was unrelated to the TNM stage, suggesting that the current stage criteria might not suitable for this lesion. Patients with MCRCC have an excellent prognosis; thus, the follow-up interval after surgery can be longer to minimize unnecessary examinations. Source of Funding: National Natural Science Foundation of China (Grant 81172418) and Beijing Municipal Natural Science Foundation (Grant 7142160).

PD55-06 PSA VELOCITY IN MEN STARTING 5-ALPHA-REDUCTASE INHIBITORS AT THE TIME OF STARTING ACTIVE SURVEILLANCE IS A PREDICTOR OF PATHOLOGICAL PROGRESSION IN LOW-RISK PROSTATE CANCER

METHODS: We investigated our institutional database of 990 men on AS between 1997-2014. Our guidelines for AS eligibility, formalized in 2008, include Gleason 6, stage cT2a, PSA 10 ng/mL, 3 of 12 cores positive at diagnosis, and 20% of any core involved at diagnosis. For this analysis, we defined borderline cases for AS as those patients with one or more of either Gleason score 7, PSA >10, stage cT2a, >33% of cores positive at diagnosis, or >20% of any core involved at diagnosis. Survival analyses were conducted using KaplanMeier and Cox proportional hazards. RESULTS: In the entire cohort (n1⁄4990), mean age at diagnosis was 66.9 years ( 7.9) and median PSA 5.1 (IQR 4-6.87). While the majority met all AS criteria, 310 patients (31.3%) met at least one of the borderline AS criteria; 2.4% of patients had Gleason 7, 7.6% had PSA >10, 8.0% were cT2a, 3.9% (37/943) had >33% of cores positive at diagnosis, and 18.4% (156/848) had >20% of any core involved. With mean follow-up 4.5 years, univariate survival analysis demonstrated no difference in freedom from treatment (FFT) between patients with Gleason 7 vs. 6, >33% vs. 33% cores involved, or PSA >10 vs. 10. Lower FFT was noted among patients with cT2a vs. cT1c disease (62.0% vs. 70.8%, P1⁄40.04), patients with >20% vs. 20% of any core involved (61.5% vs. 71.8%, P1⁄40.009), as well as those with PSA density 0.15 vs. <0.15 (61.1% vs. 72.0%, P 1⁄4 0.0006). In multivariate analysis, >20% core involvement and PSA density 0.15 remained a significant predictor for treatment (P1⁄40.003), adjusting for PSA >10, Gleason >6, >33% cores involved, and stage. Among the 310 borderline AS cases, there were only 6 (1.9%) cases of metastasis and 1 (0.3%) prostate cancer-specific death. These adverse outcomes were equivalent to the remainder of the cohort meeting strict AS criteria, which included 10 (1.5%) cases of metastasis and 2 (0.3%) prostate cancer-specific deaths. CONCLUSIONS: Active surveillance remains a viable option for select patients who are borderline cases per current AS criteria. However, patients with higher volume disease and higher PSA density may be more likely to progress to treatment. Long-term clinical outcomes in these patients should continue to be investigated.

PD03-04 LONG-TERM ONCOLOGIC OUTCOMES OF RADICAL PROSTATECTOMY IN A LARGE COHORT OF PATIENTS ON ACTIVE SURVEILLANCE

with detailed and validated clinicopathologic data for all patients with newly-diagnosed CaP. For this analysis, we identified all men who underwentRP for clinically low-riskCaP (defined as clinical stage T1 or T2a, prostate specific antigen (PSA) <10 ng/mL, and biopsy Gleason score 6) from 1/2011 through 8/2015. We compared differences in the frequency of adverse pathologic outcomes (e.g., Gleason score upgrading, seminal vesicle involvement, positive surgical margins) among patients selecting initial RP versus initial AS with subsequent transition to RP. RESULTS: During this interval, 2,858 patients with low-risk CaP were entered into the MUSIC registry. Among this group, 778 (27%) and 1,359 (48%) patients selected initial RP and initial AS, respectively. AS patients were older (63.4 vs. 60.1 years, p<0.001) with similar PSA levels (5.4 vs. 5.0 ng/mL, p1⁄40.08 for initial AS and RP groups, respectively), but less likely to have clinical T2a disease (5.1% vs 14.5%, p1⁄40.02). Among the AS cohort, the median follow-up was 506 days (IQR 280-793 days), and 79 (5.8%) transitioned to RP. Men managed with initial AS were more likely to have a pathological Gleason Score 7; however there were no other differences between these groups with respect to adverse pathology outcomes (Table 1). CONCLUSIONS: Patients with low risk CaP that enter AS have higher grade disease at RP compared to those undergoing initial RP. The lack of differences in other pathologic outcomes suggests that the surveillance process may be appropriately identifying patients with more aggressive cancers prior to stage progression.

MP42-01 NO SIGNIFICANT IMPROVEMENT IN PATIENT OUTCOMES WHEN STRICTER ACTIVE SURVEILLANCE CRITERIA ARE APPLIED: A COMPARISON OF CONTEMPORARY ACTIVE SURVEILLANCE PROTOCOLS

INTRODUCTION AND OBJECTIVES: Activesurveillance (AS) is of growing interest as an alternative to radical treatment of low-risk prostate cancer (PCa). However various surveillance eligibility criteria and protocols exist with no consensus among stakeholders as to which criteria and protocol yield the best results for the most patients. Our aim is to discern between the outcomes of stricter versus more inclusive AS protocols and elucidatewhether oneprovidesmore favorable outcomes formost patients. METHODS: Between 1998-2014, 912 men enrolled in an AS program at Princess Margaret Cancer Centre (PM) between, with the following inclusioncriteria:PSA 10, clinical stage cT2,Gleasonsum 6, number of positive cores 3, no single core>50% involved, age 75 years. All patients who met the set criteria were retrospectively reviewed and assessed for entry eligibility into: Prostate Cancer Research International: Active Surveillance (PRIAS), John Hopkins Medical Institute (JH), University of Miami (UM), University of California, San Francisco (UCSF), Memorial Sloan-Kettering Cancer Center (MSK) and University of Toronto (UT).We also considered how the use of the various protocols would alter the timing and utilization of curative intervention. Univariate and multivariate statistics with Cox proportional hazards were used for comparisons. Logistic regression was used to determine any significant associations. All statistical analysis was done using SAS . RESULTS: From 912 men enrolled over the 16 year period, 712 met PM inclusion criteria. When JH, PRIAS, and UM criteria were applied to these patients 13.7%, 11.5%, and 8.8% of these men were excluded from AS. However, when we compared outcomes such as grade or volume progression there were no significant differences between men who met the PM criteria and those who met stricter AS criteria. No significant differences in PSA velocity, or the number of patient who proceeded to seek treatment (p>0.1). Time to treatment and follow-up were also not significantly different between men who were followed on a more inclusive versus more exclusive AS protocols. CONCLUSIONS: While there are differences in inclusion criteria for AS, our results demonstrate that more strict criteria do not significantly improve patient outcomes when considering relative risk of Gleason Score upgrading, or biochemical failure after treatment. In an era of heightened awareness regarding over-diagnosis and overtreatment of prostate cancer, we believe that these stricter entry criteria should be reconsidered.