Lisa Martin

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.

Identifying the use and barriers to the adoption of renal tumour biopsy in the management of small renal masses

INTRODUCTIONnRenal tumour biopsies (RTBs) can provide the histology of small renal masses (SRMs) prior to treatment decision-making. However, many urologists are reluctant to use RTB as a standard of care. This study characterizes the current use of RTB in the management of SRMs and identifies barriers to a more widespread adoption.nnnMETHODSnA web-based survey was sent to members of the Canadian and Quebec Urological Associations who had registered email address (n=767) in June 2016. The survey examined physicians practice patterns, RTB use, and potential barriers to RTB. Chi-squared tests were used to assess for differences between respondents.nnnRESULTSnThe response rate was 29% (n=223), of which 188 respondents were eligible. A minority of respondents (12%) perform RTB in >75% of cases, while 53% never perform or perform RTB in <25% of cases. Respondents with urological oncology fellowship training were more likely to request a biopsy than their colleagues without such training. The most frequent management-related reason for not using routine RTB was a belief that biopsy wont alter management, while the most frequent pathology-related reason was the risk of obtaining a false-negative or a non-diagnostic biopsy.nnnCONCLUSIONSnAdoption of RTBs remains low in Canada. Concerns about the accuracy of RTB and its ability to change clinical practice are the largest barriers to adoption. A knowledge translation strategy is needed to address these concerns. Future studies are also required in order to define where RTB is most valuable and how to best to implement it.

Impact of Abiraterone Acetate and Enzalutamide on Symptom Burden of Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer

AIMSnTreatments and disease burden of metastatic castration-resistant prostate cancer (mCRPC) considerably affect a patients quality of life. However, patient-reported symptom burden data are still largely insufficient. This study sought to compare the self-reported symptom burden of men with chemotherapy-naive (CN) mCRPC treated with abiraterone acetate (AA) or enzalutamide (EZ) in routine clinical practice.nnnMATERIALS AND METHODSnBetween 2011 and 2015, 189 CN-mCRPC patients who had received AA (nxa0=xa076) or EZ (nxa0=xa0113) at the Princess Margaret Cancer Centre were included. The Edmonton Symptom Assessment System (ESAS) score, baseline demographic information, comorbidities, Eastern Cooperative Oncology Group performance status, laboratory data and narcotic analgesic use were recorded for each patient. The minimal clinically important difference was assessed using ±1 point change from baseline for each ESAS symptom. Mixed model for repeated measures (MMRM) was used to estimate and compare the longitudinal ESAS score changes from baseline in AA and EZ groups adjusted for age, baseline ESAS scores, treatment group, treatment duration and time.nnnRESULTSnThe median (interquartile range) treatment duration with AA and EZ was 10 (6-16) and 12 (7-18) months, respectively (Pxa0=xa00.19). Fatigue was rated the most distressing symptom at baseline and following treatment in both groups. There were no statistically significant differences in the proportion of patients with clinically meaningful symptom improvement or worsening after AA or EZ administration in any of the ESAS-based physical and psychological symptoms over time. In MMRM analyses, there were no significant differences in adjusted mean scores from baseline to 3, 6, 9 and 12 months for any of the ESAS items between AA and EZ groups.nnnCONCLUSIONnPhysical and psychological symptoms assessed by ESAS were comparable in CN-mCRPC men treated with AA or EZ in the real-world clinical setting. Further studies are warranted to confirm these findings.

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.

The origins of breast cancer associated with mammographic density: a testable biological hypothesis

BackgroundOur purpose is to develop a testable biological hypothesis to explain the known increased risk of breast cancer associated with extensive percent mammographic density (PMD), and to reconcile the apparent paradox that although PMD decreases with increasing age, breast cancer incidence increases.MethodsWe used the Moolgavkar model of carcinogenesis as a framework to examine the known biological properties of the breast tissue components associated with PMD that includes epithelium and stroma, in relation to the development of breast cancer. In this model, normal epithelial cells undergo a mutation to become intermediate cells, which, after further mutation, become malignant cells. A clone of such cells grows to become a tumor. The model also incorporates changes with age in the number of susceptible epithelial cells associated with menarche, parity, and menopause. We used measurements of the radiological properties of breast tissue in 4454 healthy subjects aged from 15 to 80+u2009years to estimate cumulative exposure to PMD (CBD) in the population, and we examined the association of CBD with the age-incidence curve of breast cancer in the population.ResultsExtensive PMD is associated with a greater number of breast epithelial cells, lobules, and fibroblasts, and greater amounts of collagen and extracellular matrix. The known biological properties of these tissue components may, singly or in combination, promote the acquisition of mutations by breast epithelial cells specified by the Moolgavkar model, and the subsequent growth of a clone of malignant cells to form a tumor. We also show that estimated CBD in the population from ages 15 to 80+ years is closely associated with the age-incidence curve of breast cancer in the population.ConclusionsThese findings are consistent with the hypothesis that the biological properties of the breast tissue components associated with PMD increase the probability of the transition of normal epithelium to malignant cells, and that the accumulation of mutations with CBD may influence the age-incidence curve of breast cancer. This hypothesis gives rise to several testable predictions.

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.

Mammographic density, blood telomere length and lipid peroxidation

Extensive mammographic density is a strong risk factor for breast cancer, but may also be an indicator of biological age. In this study we examined whether mammographic density is related to blood telomere length, a potential marker of susceptibility to age-related disease. We measured mammographic density by a computer assisted method and blood telomere length using a validated PCR method. Urinary malondialdehyde (MDA), a marker of lipid peroxidation, was measured in 24u2009hour urine collections. In the 342 women examined telomere length was negatively correlated with age, was lower in postmenopausal compared to premenopausal women and in smokers compared to non-smokers, and was positively correlated with urinary MDA. Telomere length was not associated with percent mammographic density or dense area, before or after adjustment for risk factors and MDA. However, there was a significant interaction between telomere length and MDA in their association with mammographic density. At lower levels of MDA, mammographic density and telomere length were inversely associated; while at high levels of MDA, there was evidence of a J-shaped association between mammographic density and telomere length. Further work is need to replicate these results and to examine the association of mammographic density with age-related chronic disease and mortality.