Faculty Bibliography

OBJECTIVE:To provide insights into the long-term impact of radical retro-pubic prostatectomy (ORRP) on LUTS which are age and prostate dependent and adversely impact quality of life. METHODS:1,995 men undergoing ORRP enrolled in a prospective longitudinal outcomes study. The American Urological Association symptom index (AUASI) was self-administered before ORRP and at pre-determined time-points after surgery. A multivariate generalized linear model was used to evaluate the association of time since ORRP with AUASS. McNemar's test and paired sample t-tests were used to assess whether the proportion of men with clinically significant LUTS (CSLUTS) defined by an American Urological Association symptom score (AUASS) >7 or mean AUASS differed significantly between the time-dependent assessments, respectively. RESULTS:The 15 year mean adjusted AUASS was similar to baseline (7.00 vs. 6.85, p=0.66). Throughout the 15 years of follow-up, the proportion of men with CSLUTS was lower than baseline with the exception of the 3 month and 15 year assessments. Among men with baseline clinically insignificant LUTS (CILUTS), the mean adjusted AUASS at 15 years was significantly greater than baseline (6.09 vs. 3.19, p<0.001). Among men with baseline CSLUTS, ORRP led to a significant decrease in mean adjusted AUASS between baseline and 15 years (13.26 vs. 8.67, p<0.001). CONCLUSIONS:ORRP favorably affects the long-term natural history of LUTS. The long-term economic and quality of life benefits of ORRP on LUTS should inform the risks and benefits of RP for treatment of localized prostate cancer.

PURPOSE/OBJECTIVE:To examine the time dependent rates of urinary continence (UC) following open retropubic radical prostatectomy (ORRP). MATERIALS AND METHODS/METHODS:1,995 men undergoing RP were enrolled in a prospective, longitudinal outcomes study. The University of California, Los Angeles-Prostate Cancer Index Urinary Function Index (UCLA-PCI-UFS) was administered at baseline, 3, 6, 12, 24, 96, 120, and 180 months post-ORRP. Urinary continence was defined by <1 pad in 24 hours. Two multiple regression models were used to evaluate the association of time since ORRP with UCLA-PCI-UFI score and UC. RESULTS:The decrease in UC rates between baseline and 15 years (99.6% vs. 87.2%, p<0.001) and 2 and 15 years (95.3% vs. 87.2%, p=0.021) were statistically significant. UC rates were consistently higher in the younger group at all time points. CONCLUSION/CONCLUSIONS:A significant decrease in UC rates was observed between baseline to 2 years and 2 to 15 years for the entire cohort. UC rates for age-matched men in the general population followed longitudinally for 15 years are comparable to our study population suggesting that while ORRP causes primarily sphincteric urinary incontinence, it may be protective for subsequent BPH mediated urinary incontinence.

Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo(a)pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver. TS does not induce the BP- and NNK-DNA adducts in lung, heart, liver, and bladder. TS also reduces DNA repair activity and the abundance of repair proteins, XPC and OGG1/2, in lung tissues. These TS effects were greatly reduced by diet with polyphenols. We found that γ-OH-PdG and α-methyl-γ-OH-PdG are the major adducts formed in tobacco smokers' buccal cells as well as the normal lung tissues of tobacco-smoking lung cancer patients, but not in lung tissues of nonsmokers. However, the levels of BP- and NNK-DNA adducts are the same in lung tissues of smokers and nonsmokers. We found that while BP and NNK can induce BPDE-dG and O⁶-methyl-dG adducts in human lung and bladder epithelial cells, these inductions can be inhibited by acrolein. Acrolein also can reduce DNA repair activity and repair proteins. We propose a TS carcinogenesis paradigm. Aldehydes are major TS carcinogens exerting dominant effect: Aldehydes induce mutagenic PdG adducts, impair DNA repair functions, and inhibit many procarcinogens in TS from becoming DNA-damaging agents.

BACKGROUND:There is no consensus regarding how to assess oncological control following focal ablation of prostate cancer. OBJECTIVE:To assess quality of life and in-field recurrence following focal laser ablation (FLA). DESIGN, SETTING, AND PARTICIPANTS/METHODS:Of 34 men participating in a prospective outcomes study following FLA, 32 underwent prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) at 6 mo and 2 yr. All underwent assessment of urinary and sexual function at 1 yr. INTERVENTION/METHODS:FLA and MRI-targeted biopsy of the ablation zone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:The American Urological Association Symptom Score and the Sexual Health Inventory for Men at baseline and 12 mo were compared using a two-sided Wilcoxon signed-rank test with a significance level of p=0.05. The percentage of positive and negative in-field biopsies was calculated for suspicious and nonsuspicious post-ablation MRI scans. RESULTS AND LIMITATIONS/CONCLUSIONS:FLA was associated with no adverse impact on urinary or sexual function. For men with suspicious MRI (MRI+) findings, in-field disease recurrence of intermediate and low risk disease was detected in 75% and 25% of cases, respectively. For men with nonsuspicious MRI (MRI-) findings, in-field disease recurrence of intermediate- and low-risk disease was detected in 22.4% and 50% of cases, respectively. The change in PSA from baseline did not discriminate cases with MRI- findings with and without cancer at 2 yr. CONCLUSIONS:MRI reliably identifies in-field recurrence of only intermediate-risk prostate cancer at 2 yr after FLA. A biopsy of the ablation zone must be performed for MRI+ findings. The decision to perform an ablation-zone biopsy for men with MRI- scans should be influenced by whether detection of low-risk disease would influence management. PATIENT SUMMARY/UNASSIGNED:Our study provides compelling evidence that men should undergo interval magnetic resonance imaging to assess the probability of intermediate-risk disease in the ablation zone following focal laser ablation of localized prostate cancer.

Background/UNASSIGNED:Active surveillance (AS) is the most rapidly expanding management option for favorable-risk prostate cancer (PCa). Early studies suggested substantial decrements in utility (quality of life weights) from disease-related anxiety. Our objective was to determine utilities for contemporary AS patients using different instruments. Methods/UNASSIGNED:We performed a systematic review of PubMed, PMC and OVID for utility measurements in modern AS patients. We then examined utilities among 37 men on AS participating in focus groups between 2015-2016 using the generic EurQol five dimensions questionnaire (EQ-5D-3L) and Patient Oriented Prostate Utility Scale (PORPUS), a PCa-specific instrument. Results/UNASSIGNED:The systematic review found previous studies with utilities for PCa treatment and historical watchful waiting populations, but none specifically in contemporary AS. In our AS population, the mean EQ-5D-3L score was 0.90±0.16 (median, 1.00; range, 0.21-1.00) and PORPUS was 0.98±0.03 (median, 0.99; range, 0.84-1.00). The Spearman correlation between the EQ-5D-3L and PORPUS was 0.87 (P<0.0001), and 38% of patients had a difference >0.1 between instruments. Conclusions/UNASSIGNED:Most contemporary AS patients had high utility scores suggesting that they perceive themselves in good health without a major decrement in quality of life from the disease. However, some patients had substantial differences in utility measured with generic versus disease-specific instruments. Further study is warranted into the optimal instrument for utility assessment in contemporary AS patients.

E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.

OBJECTIVE:To understand the informational needs during active surveillance (AS) for prostate cancer from the perspectives of patients and providers. METHODS:We conducted seven focus groups with 37 AS patients in two urban clinical settings, and 24 semi-structured interviews with a national sample of providers. Transcripts were analyzed using applied thematic analysis, and themes were organized using descriptive matrix analyses. RESULTS:We identified six themes related to informational needs during AS: 1) more information on prostate cancer (biopsy features, prognosis), 2) more information on active surveillance (difference from watchful waiting, testing protocol), 3) more information on alternative management options (complementary medicine, lifestyle modification), 4) greater variety of resources (multiple formats, targeting different audiences), 5) more social support and interaction, and 6) verified integrity of information (trusted, multidisciplinary and secure). CONCLUSIONS:Patients and providers described numerous drawbacks to existing prostate cancer resources and a variety of unmet needs including information on prognosis, AS testing protocols, and lifestyle modification. They also expressed a need for different types of resources, including interaction and unbiased information. PRACTICAL IMPLICATIONS/CONCLUSIONS:These results are useful to inform the design of future resources for men undergoing AS.

OBJECTIVE: To determine if multiparametric MRI (mpMRI) identifies significant apical disease, thereby informing decisions regarding preservation of the membranous urethra. MATERIALS AND METHODS: Men undergoing radical prostatectomy between January 2012 and June 2016 who underwent a 12-core transrectal-ultrasound guided systematic biopsy, preoperative 3-T MRI, and sectioning of the prostate specimen with tumor foci mapping were extracted from a single surgeon's prospective longitudinal outcomes database. Apical systematic biopsy vs. mpMRI lesion were compared for predicting aggressive tumor in the prostatic apex defined as Prostate Cancer Grade Group >1. RESULTS: Of the 100 men who met eligibility criteria, 43 (43%) exhibited aggressive prostate cancer in the distal 5mm of the apex. A Likert score > 2 in the apical one-third of the prostate was found to be more reliable than any cancer found on apical systematic biopsy at detecting aggressive cancer in the apex. On multivariate regression that included Likert score in the apex, age, PSA, prostate size, and presence of any cancer on apical biopsy, only Likert score (p=.005) and PSA (p=.025) were significant and independent predictors of aggressive cancer in the distal apex. CONCLUSION: MRI is superior to systematic biopsy at identifying aggressive prostate cancer within the distal prostatic apex and may be useful for planning the extent of apical preservation during prostatectomy.