Moreira, Daniel M.

Objectives To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. Patients and Methods We performed a review of 1 808 consecutive men referred for elevated prostate‐specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. Results The MRI and PSA‐only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA‐only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group ( P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA‐only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29–2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48–2.80; P < 0.001) were higher in the MRI than in the PSA‐only group after adjusting for clinically relevant PCa variables. Conclusion Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

Objective To evaluate biochemical recurrence ( BCR ) patterns amongst men undergoing radical prostatectomy ( RP ) with specimens having negative ( NSM ), positive ( PSM ), and close surgical margins ( CSM ) from the Shared Equal Access Regional Cancer Hospital ( SEARCH ) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. Patients and Methods Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM , PSM , and CSM . CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate‐specific antigen ( PSA ) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR , metastases, and mortality were analysed using Cox proportional hazard models. Results Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM , 1902 (44%) had PSM , and 372 (8%) had CSM . On multivariable analysis, relative to NSM , men with CSM had a higher risk of BCR (hazard ratio [ HR ] 1.51, 95% confidence interval [ CI ] 1.25–1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM ( HR 2.09, 95% CI 1.86–2.36; P < 0.001). Metastases, prostate cancer‐specific mortality and all‐cause mortality did not differ based on margin status alone. Conclusions Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

420 Background: Cytoreductive nephrectomy (CN) has been associated with significant morbidity, but there is little data identifying patients at increased risk. We evaluated the association of clinicopathologic features with early post-operative complications and prolonged length of stay (pLOS) among CN patients. Methods: We identified 294 patients treated with radical nephrectomy for M1 renal cell carcinoma between 1990 and 2009 at the Mayo Clinic. All complications within 30 days of surgery were reported using standardized methodology according to the Clavien classification. Associations with the presence of any early complication and pLOS (defined as ≥8 days, the top 25th percentile) were evaluated using logistic regression models. Results: Thirty-five (12%) patients experienced at least one early complication and 15 (5%) patients experienced at least one Clavien grade ≥3 early complication. The median LOS was 6 days (IQR 5-7), and 68 (23%) patients had a pLOS. On univariate analysis, liver metastases, symptomatic presentation, intraoperative transfusion, and pathologic nodal stage were significantly associated with both early complications and pLOS (Table). Two multivariate models were constructed. In Model 1 (limited to pre-operative features), only liver metastases (p<0.01) were associated with early complications while liver metastases (p=0.01) and open approach (p=0.02) were associated with pLOS. In Model 2 (all variables included), liver metastases (p=0.01), intraoperative transfusion (p<0.01), and high nuclear grade (p<0.01) were associated with early complications while intraoperative transfusion (p<0.01) and positive nodes (p=0.05) were associated with pLOS. Conclusions: CN was associated with a low incidence of early post-operative complications, particularly Clavien ≥3 complications. Presence of liver metastases and intraoperative transfusion were independently associated with increased risk of both complications and pLOS. [Table: see text]

23 Background: Perineural invasion (PNI) on prostate cancer (PC) biopsies has been associated with disease upgrading among those undergoing radical prostatectomy. However, the clinical significance of PNI in men on active surveillance (AS) has been evaluated by a limited number of studies. Thus, we sought to evaluate the association of PNI with time to clinical and pathological progression in men with PC on AS. Methods: Retrospective analysis of 289 men 48 to 82 years old on AS for low-risk PC (T1c-T2a), Gleason ≤6, ≤3 positive cores, ≤50% of any core involved, prostate-specific antigen (PSA) ≤11ng/ml, life expectancy >5 years and follow-up data in the REduction by Dutasteride of clinical progression Events in Expectant Management study. Progression was divided in pathological (>3 positive cores, >50% core involvement or Gleason >6 in a repeat biopsy) or therapeutic (any treatment for PC) or both. Time to progression was analyzed with Kaplan-Meier plots, log-rank tests and Cox model adjusting for age, PSA density, percent cores involved, maximum core involvement and treatment. Results: A total of 11 (4%) patients had PNI on baseline biopsy. PNI was associated with higher tumor length and maximum core involvement (all P<0.05). PNI was not associated with patient’s age, race, PSA levels or density, percent or number of positive cores. After a median follow-up of 37 months, 125 (43%) patients developed progression. Of these, 95 (76%) patients had pathological and 30 (24%) had therapeutic progression. In univariable analysis, patients with baseline PNI had a shorter time to overall and pathological progression (HR=2.62, 95%CI=1.31-5.23, P=0.006 and HR=2.42, 95%CI=1.03-5.66, P=0.041, respectively). Similar results were obtained in multivariable analysis for overall and pathological progression (HR=2.26, 95%CI=1.10-4.68, P=0.028 and HR=2.13, 95%CI=0.88-5.13, P=0.092, respectively). Conclusions: Among patients with PC on AS, PNI is independently associated with shorter time to progression. Thus, PNI may be used to help select patients for AS and stratify them according to the risk of disease progression.

75 Background: We have previously shown that chronic baseline prostate inflammation in an otherwise benign biopsy was associated with lower risk of prostate cancer in repeat prostate biopsies and lower tumor volumes for those who are diagnosed with cancer. In the present study, we evaluated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 889 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for prostate cancer in the REDUCE study. Acute and chronic prostate inflammation (coded as present or absent) and cancer grade were determined by central pathology. The association of inflammation in baseline biopsies with 2-year repeat biopsy cancer grade (low-grade: Gleason scores 2-6 vs. high-grade: Gleason scores 7-10) was evaluated with t test, chi-squared test and logistic regression controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline pre-study PSA and treatment (dutasteride or placebo). Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammations were significantly associated with each other (P < 0.001). Patients with chronic inflammation had significantly larger prostates (P < 0.001). Both types of inflammation were unrelated to race, BMI, PSA or DRE. At 2-year biopsy, a total of 621 (70%) tumors were low-grade and 268 (30%) tumors were high-grade. In both uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable OR = 0.64, 95% CI = 0.47-0.87, P = 0.004; multivariable OR = 0.68, 95% CI = 0.50-0.93, P = 0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade. Conclusions: Among men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy who all had cancer on the follow-up biopsy, the presence baseline chronic inflammation was associated with lower prostate cancer grade.

6 Background: Study compliance is crucial when the study outcome is determined by an invasive procedure, such as prostate biopsy. To investigate predictors of compliance in study-mandated prostate biopsies, we analyzed demographic, clinical and reported lifestyle data from the REDUCE trial. Methods: We retrospectively identified 8,062 men from REDUCE with at least 2-years of follow-up, and used multivariable logistic regression to test the association between baseline demographic and clinical characteristics and undergoing the study-mandated prostate biopsy at 2 years. We then examined whether missing any of these data was associated with undergoing a biopsy. Results: In REDUCE, 20% of men did not undergo a 2-year biopsy.On multivariable analysis, non-North American region was predictive of 35-55% increased likelihood of undergoing a 2-year biopsy (p ≤ 0.001). Being enrolled at a center that enrolled >10 subjects (2nd and 3rd tertile) was associated with a 40-49% increased likelihood of undergoing a 2-year biopsy (p < 0.001). Missing one or more baseline variables was associated with a 25% decreased likelihood of undergoing a 2-year biopsy (OR = 0.75; p = 0.002). Conclusions: In REDUCE, men outside North America, those at higher volume centers, and those with complete baseline data were more likely to undergo study mandated 2-year biopsies. Given prostate biopsy is becoming increasingly utilized as an endpoint in trials that are often multi-national, regional differences in compliance should be considered when designing future trials. Likewise, efforts are needed to ensure compliance in low-volume centers or among subjects missing baseline data.

122 Background: We have previously shown baseline prostate atrophy (PA) was independently associated with lower prostate cancer (PC) risk. Beyond PC risk, for those who develop PC it is unclear whether PA is associated with smaller, less aggressive and/or less advanced tumors. Thus, we evaluated whether baseline PA and PA severity in men with initial negative biopsy for PC was associated with PC volume at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 763 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for PC with complete data in the REDUCE study. Presence and severity of PA, and tumor volume were determined by central pathology. The association of PA at baseline biopsies with 2-year repeat biopsy cancer volume variables was evaluated with linear and Poisson regressions and controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline and pre-repeat biopsy prostate-specific antigen (PSA) and treatment arm. Results: PA was detected in 458 (60%) baseline biopsies and was considered mild in 398 (87%) and moderate in 60 (13%) cases. Patients with PA had significantly larger prostates and lower baseline and pre-repeat biopsy PSA (P < 0.01). PA was unrelated to race, BMI, DRE or treatment arm. At 2-year biopsy, men with baseline PA had significantly lower overall mean total tumor volume (2.04µL vs 3.02µL; P = 0.006), mean number of biopsy cores involved (1.79 vs 2.11; P = 0.001), mean percent of cores involved (17.9% vs 21.2%; P = 0.001), average core involvement (0.20µL vs 0.30µL; P = 0.001) and overall mean percent tumor involvement (1.64% vs 2.35%; P = 0.006) than those without PA. The results were virtually unchanged in multivariable analysis (all P < 0.05 except for overall percent tumor involvement where P = 0.061). In the analysis of PA severity, a biological gradient was observed where moderate PA was associated with greater reduction in tumor volume compared to mild PA (data not shown). Conclusions: In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline PA was associated with lower PC volume. These results suggest PA may be associated with less aggressive PC.

116 Background: Prostateinflammation is linked with prostate cancer. However, whether prostate inflammation varies by race is unclear. Methods: We analyzed baseline acute and chronic prostate inflammation by race in REDUCE. REDUCE was a 4-year, multicenter, placebo-controlled study where all men received a single, negative prostate biopsy within 6 months prior to enrollment. Among 8,046 men who met the inclusion criteria, we included those with data on baseline biopsy prostate inflammation, acute/chronic or none, determined by central pathology. Logistic regression was used to compare prostate inflammation by race, and models were adjusted for demographic and clinical features. Results: Of the 8,046 men, 7,326 were white (91.1%), 184 (2.3%) black, 132 (1.6%) Asian, 323 (4.0%) Hispanic, and 81(1%) unknown. Seventy eight percent of men had chronic and 15% had acute prostate inflammation. Men with chronic inflammation were older (p<0.001), while men with acute inflammation were younger (p<0.001) compared to men with none prostate inflammation. Both acute and chronic inflammation was associated with lower PSA (all p≤0.0001), smaller prostate volume (all p≤0.0001) and geographic region (all p≤0.006). On crude analysis, compared to whites, Asian men were two times more likely to have acute prostate inflammation (OR=1.92, 95%CI: 1.29-2.85, p=0.001), whereas the associations with Hispanic and black race were not significant (all p≥0.39). However, on multivariable analysis, black men were 36% less likely to have acute prostate inflammation (OR=0.64, 95%CI: 0.41-0.99, p=0.04), whereas the likelihood of having acute prostate inflammation remained high in Asians (OR=1.85, 95%CI: 1.25-2.85, p=0.004). No associations by race were found with chronic prostate inflammation. Conclusions: Given that at the population level, black race is a high risk factor for PC and Asian men have lower risk of PC, these data indicate that the presence of acute inflammation in a negative prostate biopsy could be an indication of future PC risk. Further studies to confirm these findings are needed. Clinical trial information: NCT00056407.